Final Evaluation Report | Global Station for Zoonosis Control, GI-CoRE, Hokkaido University

Global Station for Zoonosis Control
Global Institution for Collaborative Research and Education(GI-CoRE)
Hokkaido University

Final Evaluation Report

北海道大学

国際連携研究教育局

人獣共通感染症グローバルステーション

外部評価報告書

July 2020

July 2020
2020 年 7 月

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Final Evaluation Report(brief version in Japanese)
外部評価報告書（日本語・概要版）

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もくじ（日本語版）

はじめに •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 5
外部評価委員 ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 7
外部評価委員会実地調査要領••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 8
外部評価調書の概要 ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 9

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はじめに
国際連携研究教育局（GI-CoRE）は、北海道大学の強みや特色を活かした国際連携
研究教育の推進と、部局が独自に進める国際連携研究教育の支援を目的とし、世界トップレベルの教員を国内外及び学内から結集した総長直轄の教員組織です。
GI-CoRE 内には研究領域ごとの活動拠点である「グローバルステーション（GS）」
を置き、各 GS において、原則 5 年間の設置期間内に重点的に研究教育活動を進めています。これまでに、延べ７つの GS（下記※を参照）を設置し、研究活動を推進するとともに、最先端の研究成果を大学院教育などに還元してきました。
GI-CoRE では、GS の設置期間満了を迎える年度に、各 GS でのこれまでの活動を振り返るとともに、今後、より強固かつ持続可能な研究教育体制を確立していくため、
国内外の有識者により構成される外部評価委員会において、評価を実施することとしています。
この外部評価報告書は、2018 年 7 月に実施した人獣共通感染症 GS の自己点検成果
報告書及び外部評価結果を一冊に収録した、いわば GS の研究教育活動の集大成です。
なお、設置期間を満了した人獣共通感染症 GS は、関連部局等に定着化し、2020 年
4 月以降も「GI-CoRE 協力拠点」として、GI-CoRE と連携しながら研究教育活動を継続
しています。
本学では、外部評価結果を踏まえ、より充実した研究教育活動を実践していくこと
により、世界の課題解決に貢献していきたいと考えております。

北海道大学 国際連携研究教育局
局長代行（総長代行）
笠 原 正 典※これまでに設置したグローバルステーション（GS）
GS 名

設置期間

主な学内連携部局等（年度）
量子医理工学2014～2019

医学研究院、大学病院ほか

人獣共通感染症

2014～2019

人獣共通感染症リサーチセンター、獣医学研究院

食水土資源

2015～2019

農学研究院ほか

ソフトマター2016～2020

先端生命科学研究院ほか

ビッグデータ・サイバーセキュリティ

2016～2020

情報科学研究院ほか

北極域研究2016～2020

北極域研究センターほか

バイオサーフィス創薬

2019～2023

薬学研究院ほか

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国際連携研究教育局(GI-CoRE)
人獣共通感染症グローバルステーション
外部評価委員*国際医療福祉大学塩谷病院

倉田

毅

教授

アメリカ合衆国

セント・ジュード小児研究病院

オーストラリアモナシュ大学

ベン・アドラー

ロバート・ウェブスター教授
名誉教授

*委員長

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国際連携研究教育局(GI-CoRE)
人獣共通感染症グローバルステーション
外部評価委員会実地調査要領

１．調査日程平成 30（2018）年 7 月 19 日（木）～20 日（金）２．詳細スケジュール
7 月 19 日（木）13:30～14:30

趣旨説明・笠原 GI-CoRE 副局長（理事・副学長）との懇談

14:50～15:20

施設見学（人獣共通感染症リサーチセンター）

7 月 20 日（金）14:00～15:30

関係教員のヒアリング

15:30～16:30

評価委員の打合せ

16:30～17:00

評価委員による講評

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国際連携研究教育局(GI-CoRE)
人獣共通感染症グローバルステーション
外部評価調書の概要（参考和訳）

総合評価：Ｓ（評価コメント）
新興感染症の多くは人獣共通感染症である。北海道大学 GI-CoRE 人獣共通感染症グローバ
ルステーション（GSZ）は、国際社会の課題である人獣共通感染症の克服に向け、極めて優れた対策を推進している世界に類のない組織であり、内外に高く評価されている。 また、GSZ
は“One Health-One World”の概念の下、獣医学、医学、生態学分野を融合した新学術領域を創成し、人獣共通感染症の早期発見とその抑制に向けた、予防、診断、治療法の開発および、宿主間伝播機構の解明を目的とする国際連携研究プログラムを遂行している。さらに、
人獣共通感染症対策に資する人材育成を目指して、国際感染症学院を創設し、また博士課程
大学院生を対象とした教育プログラムを推進している。
GSZ は世界トップレベルの研究者を、国内外から招聘することにより、人獣共通感染症の研究、教育、国際連携ネットワークの構築を達成している。ジカ熱等の新興感染症を対象とした研究も、国内外の研究者との共同研究により推進している。人獣共通感染症の発生が多い
発展途上国との共同研究を重視し、アジア、アフリカ、南アメリカにおける研究を進めており、GSZ を中心とする国際共同研究は世界規模となっている。GSZ の研究が世界一流であることは、高水準の学術雑誌への論文投稿、および社会への貢献から判断される。国際感染症学院でも、発展途上国出身の学生の教育を重視しており、多くの博士課程修了者を国際社会に輩出していることも高く評価される。
GSZ の推進者である喜田統括が、WHO（世界保健機関）や OIE（国際獣疫事務局）の委員を務めており、GSZ が国際社会において重要な役割を担っていること、また発展途上国における研究発展と人材育成を目的とする教育訓練の場を提供していることが評価される。
将来展望として、現在長崎大学に BSL-4 施設が建設されているが、人獣共通感染症リサー
チセンタに BSL-4 施設が必須と思われる。また、感染症発生現場で新興感染症の発生に対応できる人材を育成することを念頭に置いているので、獣医師と医師を共に募集することが必要である。
以上、総合評価において、GSZ は日本および国際社会における貢献度が高いことから「Ｓ」と判定した。
評価者は全員一致で GSZ の活動を高く評価しており、今後も GSZ が継続して貢献することを強く求める。
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Final Evaluation Report(original version in English)
外部評価報告書（英語・オリジナル版）

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Contents
Foreword •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 15
External Evaluation Committee••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 17
Schedule of the External Evaluation Committee •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 21
Results of the Evaluation Committee ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 23
Research Progress Report (2014-2019) ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 45
References ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 139

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Foreword
Hokkaido University established the Global Institution for Collaborative Research and
Education (GI-CoRE) as a faculty organization under the direct control of the President thatbrings together world-class researchers from around the world and within the University. It
aims to promote international collaborative research and education that leverages the
University’s strengths and distinctive features as well as to provide support for international
collaborative research and education promoted by faculties and centers, respectively.
Under the GI-CoRE system, a research and education hub known as a Global Station (GS) is
implemented for each research field. GSs have a finite implementation period of five (5) years
in principle to conduct intensive research and education activities. Thus far, seven (7) GSs in
total (see * below) have been implemented to further develop research activities and contributethe resulting cutting-edge research outcomes to graduate school education.
In the final year of the GI-CoRE project period, a Final Evaluation is conducted by the External
Evaluation Committee composed of global experts outside Hokkaido University for each GS
to not only review GS activities from past years but also build a stronger and more sustainable
research and education system in the future.
This Final Evaluation Report contains the Research Progress Report of GS for Zoonosis Control(GSZ) conducted in July 2018 and the evaluation results. This report is a compilation of theresearch and education activities of GSZ.
After the implementation period, GS projects are transitioned into affiliated faculties andcenters, then certified as “GI-CoRE Cooperating Hubs” to continue research and education
activities in cooperation with GI-CoRE after April 2020.
Hokkaido University remains committed to continuing its efforts to contribute to resolving
global issues by conducting advanced research and education activities based on evaluation
results.

Professor Masanori Kasahara, M.D., Ph. D.
Interim Director
Global Institution for Collaborative Research and Education (GI-CoRE)
Hokkaido University(Interim President, Hokkaido University)

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*The Global Stations (GSs) implemented thus far.
Implementation

Name of the GS
Quantum

MedicalScienceand

2014–2019

Engineering
Zoonosis Control

Main Internal Affiliation

Period (FY）

Faculty of Medicine, University Hospital,and others

2014–2019

Research Center for Zoonosis Control andFaculty of Veterinary Medicine

Food, Land and Water Resources

2015–2019

Research Faculty of Agriculture and others

Soft Matter

2016–2020

Faculty of Advanced Life Science and others

Big Data and Cybersecurity

2016–2020

FacultyofInformation

ScienceandTechnology and others
Arctic Research

2016–2020

Arctic Research Center and others

Biosurfaces and Drug Discovery

2019–2023

Faculty of Pharmaceutical Sciences andothers16

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Global Station for Zoonosis Control
Global Institution for Collaborative Research and Education(GI-CoRE)
External Evaluation Committee*Professor Takeshi Kurata,
International University of Health and Welfare, Shioya Hospital (Japan)
Professor Robert G. Webster,St. Jude Children’s Research Hospital (United States of America)
Emeritus Professor Ben Adler,
Monash University (Australia)*Chair17

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Attachment

Letter of Acceptance
23/03/2018

To Director Toyoharu Nawa of the Global Institution for Collaborative Researchand Education (GI-CoRE), the National University Corporation Hokkaido
University.

I hereby accept my appointment to serve as a member of the External
Evaluation Committee for the Global Station for Zoonosis Control at the Global
Institution for Collaborative Research and Education (GI-CoRE), Hokkaido
University.

Signature
Professor Ben Adler

Professor Ben Adler
Emeritus Professor of Microbiology
Department of Microbiology
Monash University
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Global Station for Zoonosis Control
Global Institution for Collaborative Research and Education(GI-CoRE)
Schedule of the External Evaluation Committee

1. Date of Implementation
Thursday, July 19 - Friday July 20, 2018
2. On-site Investigation ScheduleThursday, July 19
1:30pm - 2:30pm

Greeting and brief overview
from Vice Director. Masanori Kasahara, GI-CoRE
Break

2:50pm - 3:30pm

Facility tour

Friday, July 20
2:00pm - 3:30pm

Interview Session with GI-CoRE Faculty members

3:30pm - 4:30pm

Discussion among committee members

4:30pm - 5:00pm

Review from the committee to the faculty members

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Results of the Evaluation Committee

Evaluation Committee

Global Station for Zoonosis Control
Global Institution for Collaborative Research and Education (GI-CoRE)
Hokkaido University
October 201823

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Summary Report
The Global Institution for Collaborative Research and Education (GI-CoRE) Global Station for
Zoonoses Control that has been established at Hokkaido University is fulfilling an unmet global
need, and is absolutely outstanding. The program is a credit to the faculty concerned, to the
University, and is unique in the world. The recognition that most of emerging infectious
diseases of humans and domesticated animals come from environmental and zoonotic threats
is being addressed by this program. It brings together the fields of ecology, veterinary andhuman public health under the “One Health-One World” concept. The GI-CoRE program at
Hokkaido University has established international cooperative research programs elucidating
the fundamental mechanism of interhost transmission with the development of vaccines,
diagnostics and therapeutics aimed at rapidly detecting and controlling diseases that could becatastrophic. The program also recognizes the need for trained personnel and has implemented
a world class graduate program.
The program is completely meeting the goals of research, education and the establishment of aframework for international cooperative research and education. The strong points of the
program are the achievements in attracting world class researchers, both within Japan andinternationally. Cooperation between the researchers has enabled the program to address newly
emerging infectious diseases, including zika and MERS-CoV. Expansion of the program toAsia, Africa and South America with a strong focus on underdeveloped countries shows theglobal reach of the program. The high level of productivity and quality of publications in theleading scientific journals attests to the program’s high standard of research and demonstrates
that it serves society by developing strategies to rapidly control emerging infectious diseases.
The graduate school deserves special mention, for it has already graduated 19 PhDs, with astrong focus on students from international and developing countries.
Participation of the director of the GI-CoRE program in the World Health Organization (WHO),and the World Organization for Animal Health (OIE) adds to the strength of the GI-CoRE
program. The GI-CoRE program provides unique strengths and training at human-animalenvironmental interface with special emphasis on international research and training in
undeveloped countries.
Future expansion of the program would benefit from having its own BSL4 facility; while thecurrent needs of the program will be met by the BSL4 laboratory being constructed at Nagasaki,in the longer term it would be beneficial to have such a facility onsite. The recruitment ofadditional MDs would also be beneficial, especially if future goals are to provide trained
personnel to respond to emerging zoonotic disease outbreaks in the field.

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The overall evaluation is that the GI-CoRE program is outstanding (S), it serves both Japan andthe world. The reviewers’ unreservedly and enthusiastically recommend continuation of thisimportant program.

Professor Takeshi KurataInternational University for Health and Welfare
Professor Robert G. Webster
St. Jude Children’s Research Hospital
Professor Ben Adler
Monash University

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Global Station for Zoonosis Control
Global Institution for Collaborative Research and Education (GI-CoRE)
Final Evaluation
External Evaluation Committee Member Name:

Takeshi Kurata.

Choose one of the five Evaluation Ratings options below as explained by the Evaluation Explanation for each
Evaluation Item on the form.
Evaluation

Evaluation Explanation

Ratings
S

Achieved outcomes surpassed the original plan (Outstanding)A

Good progress has been maintained and expected outcomes have been achieved(Excellent)

B

Most expected outcomes have been achieved with some slight delays (Good)C

Although certain outcomes were achieved, overall results were insufficient (Satisfactory)D

No expected outcomes were achieved (Unsatisfactory)

I. Research1.

Has construction of an international research and education center capable of attracting outstanding researchers

from around the world (including from HU) been achieved?
Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons)
The Research Center for Zoonosis Control of Hokkaido University has excellent long-term collaboration
system for zoonosis control activity with 32, 6 developed and 26 developing countries. Graduated PhD students are
19, including 7 Japanese during past 4 years (2014-2018). In addition, PhD course students are 37 including 16
Japanese and 21 foreign ones. They have published excellent scientific papers on zoonosis control.
Scientific activity of the staffs at Hokkaido University Research Center for Zoonosis Control is rapidly
expanding from Asian countries to Russia, Europe, African and South American countries. The research activity
contributes much for One Health of local to worldwide. I was indeed impressed by their presentations and active
discussion made at the 6th Meeting of the Consortium for the Control of Zoonoses.
In addition, the publication record of the Research Center for Zoonosis Control is superb both in the point ofview of numbers and quality.
As a member of the present External Evaluation Committee, I learned that outstanding international

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collaborating programs are successfully ongoing in this GI-CoRE Program.
(Outstanding points)
It is surprising that first class researchers from three well known universities in the world gathered in the
Research Center for Zoonosis Control at Hokkaido University and are proceeding important programs incollaboration with the members of the Center. Researchers from the University of Melbourne are carried out withthe members of the Unit for the Development of Vaccine and Biologicals. Researchers from the University College
Dublin are collaborating with the members of the Unit for Exploration of Pathogens, and the researchers from King
Abdullah University of Science and Technology are concentrating into genome-function analyses of pathogens withthe members of the Unit of Bioinformatics.
To integrate research activities towards the goal of controlling zoonoses, the Consortium for the Control of
Zoonoses, where all three units members meet together and exchange information, has been established and is
working successfully with effective and functional manner.
(Suggestions for improvement)
No specific points for improvement.
2.

Is world-leading cutting-edge international cooperative research underway?

Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons)
Outstanding researchers, Profs H Kida, H Sawa and C Sugimoto at Hokkaido University Research Center for
Zoonosis Control, Profs DC Jackson, LE Brown and E Hartland at the University of Melbourne, Prof W Hall at the
University College of Dublin and Prof A Pain at the King Abdullah University of Science and Technology gathered
together at Hokkaido University and formed the Consortium for the Control of Zoonosis. I believe that thisconsortium is the outstanding and strongest team for the control of zoonoses in the world.
Excellent publication record also indicate that their research activity is outstanding.
Specific points(Outstanding points)
As stated above.
(Suggestions for improvement)
No specific points for improvement.

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3.

Are research outcomes from GI-CoRE being actively utilized to solve social issues?

Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons)
Identification of natural host animals of and the routes of transmission of the pathogens is the base for thecontrol of zoonoses. The members of this GI-CoRE program have been developed several cheap and conventional
diagnosis kits and methods for the detection of novel viruses and bacteria by genetic and immunologic analyses. By
using these technology, many novel viruses and antibiotic resistant mycobacteria have been found.
Specific points(Outstanding points)
Since the present Consortium is composed of first class researchers from multidisciplinary fields such as
virology, bacteriology, immunology, entomology, molecular biology, bioinformatics, ecology, pharmacology andmedical and veterinary clinics and they are cooperating effectively, the programs for the control of zoonoses are
fulfilled effectively, and thus successful.
(Suggestions for improvement)
Nothing particular.

II. Education
Is the educational system and curriculum designed to help develop researchers who possess specialized
knowledge and are capable of working internationally?
Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons)
Plans to create an educational structure and courses have been undertaken with the objective of fostering
personnel who will cope with emerging and re-emerging infectious diseases. The present GI-CoRE program islooking ahead to take steps to foster global human resources. Establishment of the Graduate School of Infectious
Diseases accelerates to strengthen and expand the educational scheme for postgraduates and develop specialists
internationally contributing to global health solutions. The Graduate School provides the opportunity to obtain
practical communication skills in English and will access the international research community consisting ofcollaborating scientists from more than 30 countries.

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Specific points(Outstanding points)
GI-CORE members are involved in educational program at the Graduate School of Infectious Disease. They
are leading world-class international experts in the research field of infectious diseases. It is assured that theyeducate students to become the next generation of leaders who have broad vision, innovative ideas and thenecessary skills to solve the problem of infectious diseases.
(Suggestions for improvement)
Current number of researchers at GI-CORE are rich in veterinary doctors, of which the reason is the Centerhas been based the part of School of Veterinary Medicine at Hokkaido University. It is recommended to invite
excellent medical researchers who can collaborate with other field scientists on zoonotic diseases in the ResearchCenter for Zoonosis Control.

III. Establishment of Framework
Are the necessary systems and frameworks being established in order to conduct international cooperative researchand education?
Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons)
The system and framework have been established at a high level by strong collaborative relationships withthree research units; the University of Melbourne, University College Dublin and King Abdullah University of
Science and Technology under the Global Station for Zoonosis Control. The Consortium for the Control of
Zoonoses consisting of four research units is working successfully on the basis of unique and outstanding concept of
GI-CoRE. The GI-CoRE management system supports the research and educational activities of Global Station for
Zoonosis Control financially and systematically.
Specific points(Outstanding points)
The GI-CoRE has an attractive system to accept world-class leading international researchers.
Implementation cross-appointment and an annual-salary system is well thought.
(Suggestions for Improvement)
Nothing particularly.

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IV. Overall Evaluation
The risks of incidence of arising emerging and re-emerging infectious diseases are increasing. More than 30
viral diseases, 15 bacterial and parasitic infectious diseases have emerged in the last 20 years. More than a half ofthe new diseases are zoonotic. One Health authorities are required urgently to increase the budgets and official
personnel to control these new emerging infectious diseases. In such circumstances, the establishment of the Global
Station for Zoonosis Control at Hokkaido University is of great significance in the research fields of infectious
diseases. The Global Station for Zoonosis Control is a unique organization that aims to conduct research andresponse to zoonosis outbreaks. The activities of research and practical counter-measures are at quite a high level ofglobal standards. Also, the Global Station for Zoonosis Control is accepting researchers and materials from over
the world. It is clear that these materials sometimes must contain high biosafety level pathogens. It is strongly
recommended that in addition to biosafety level 3 containment facility, Biosafety Level 4 facility and well-trained
experts are crucially needed at the Research Center for Zoonosis Control.
Forming a consortium to promote research and education on zoonosis control in collaboration with theresearch units, Hokkaido University, the University of Melbourne, University College of Dublin and King Abdullah
University of Science and Technology is quite nice and smart. The consortium is enhancing the collaborationof all research units for the control of zoonoses and developing measures for diagnosis, disease prevention andtherapy for infectious diseases.
Finally, the present reviewer strongly recommend for the Research Center for Zoonosis Control to establish a
BSL-4 facility as soon as possible, to ensure safer practice with any materials from abroad and to lead One HealthInstitutes in the world.
Overall, the activities of Global Station for Zoonosis Control is evaluated as outstanding without hesitation.
We are looking forward to seeing the next stage of the GI-CoRE program of excellence on their collaborative andeducational activities.

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32

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Global Station for Zoonosis Control
Global Institution for Collaborative Research and Education (GI-CoRE)
Final Evaluation
External Evaluation Committee Member Name:

Robert G. Webster.

Choose one of the five Evaluation Ratings options below as explained by the Evaluation Explanation for each
Evaluation Item on the form.
Evaluation

Evaluation Explanation

Ratings
S

Achieved outcomes surpassed the original plan (Outstanding)A

Good progress has been maintained and expected outcomes have been achieved(Excellent)

B

Most expected outcomes have been achieved with slight delays (Good)C

Although certain outcomes were achieved, overall results were insufficient (Satisfactory)D

No expected outcomes were achieved (Unsatisfactory)

I. Research1.

Has construction of an international research and education center capable of attracting outstanding researchers

from around the world (including from HU) been achieved?
Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons)
From a research perspective it is clear that an outstanding collaboration of researchers from The University of
Melbourne-Drs. Brown, Jackson, Hartland; from The University of Dublin-Drs. Hall, Carr and Gordon, and fromthe King Abdullah University of Science and Technology, Saudi Arabia- Dr. Pain, together with an impressive groupof researchers from Hokkaido University led by Professors Kida has established an outstanding collaborative
research and education programme (GI-CoRE) at Hokkaido University for zoonoses control. This collaboration
enables the researchers within and outside the university to conduct research on a wide range of emerging andreemerging infectious disease agents that are a continuing threat to veterinary and human public health, both within
Japan and globally.
(Reasons)
The coverage of environmental threats to humanity is extremely impressive, including not only the known

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environmental threats, but also the search for novel agents in Zambia, threats to public health in Nepal, Myanmar,
and Thailand as well as expansion of the program to Vietnam, Brazil and Cuba. The rapid inclusion of research on
Zika and chickungunya and the development of methodology for diagnosis by sequencing illustrating the flexibilityof the programme and inclusion of novel emerging threats.
The productivity from the international collaboration with 118 peer reviewed papers in international journals
covering the complete field of zoonotic threats attests to both the quality and the productivity at an international
level.
Specific points(Outstanding points)
The application of next generation sequencing and portable sequencing utilizing low-cost real time portablesequencing provides the possibility of rapid detection of emerging infectious agents in the field. The use of genomic
analysis to elucidate horizontal gene transfer in protozoan parasites, and elucidation of the genes in legionella thatsubvert host cell transcriptional responses attests to the wisdom of genomic analysis of emerging zoonotic agents.
An important challenge is to convince the global influenza community about the potential advantages ofmoving back to whole influenza virus vaccines which would be absolutely essential in the face of an extremely
severe influenza pandemic, there would be a great need for antigen sparing to save lives potentially in underdeveloped countries. These studies together with improved adjuvants and the ability to predict the severity of an
influenza pandemic address an unmet global need.
(Suggestions for improvement)
Overall the Consortium for the Control of Zoonoses is very and no improvement are suggested. Reducing thecosts of sequence analysis in the field is a minimal aim.
2.

Is world-leading cutting-edge international cooperative research underway?

Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons)
The productivity from the consortium members, with a high number of publications (118), the high number ofinvited oral presentations (51), patent applications (4), awards received (6), and external grants (2) attests to theworld class cutting edge cooperative research that is underway. The cooperation is attested to throughout the
program with collaborations between each of the international groups with scientists at Hokkaido University.
(Outstanding points)
Particularly good points include the genomic driven approaches in the studies of zoonotic malaria,
development of novel drugs for Ebola, and the multiple collaborations with the University of Zambia gives access

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to a potential wealth of novel agents.
(Suggestions for improvement)
The high level of productivity and the extent of international collaboration as well as the world class cuttingedge research ongoing at Hokkaido University indicates that there is little room for improvement. It is encouraging
that the difficulties encountered in the expansion of the program to Cuba are being worked through, and that this site
is being developed despite the difficulties, for Cuba represents and under evaluated global resource.
3.

Are research outcomes from GI-CoRE being actively utilized to solve social issues?

Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons)
Each of the programs in the GI-CoRE address social issues of importance related to the emergence andcontrol of zoonoses. For example the studies on the neuropathology of prion diseases has the potential to lead to atreatment of prion diseases and neurodegenerative disorders of both humans and lower animals, for these areunresolved issues. A case could be made for each and every one of the projects. An example to illustrate thecontribution to society would be the development of an anthrax vaccine; a safe and effective anthrax vaccine forhumans is not available. The studies on the dimerized PAD-1 vaccine based on computational design together with
the immuno-stimulatory molecules of the Pam2Cys from the University of Melbourne with David Jackson has thepotential for providing a safe and highly efficacious vaccine for both humans and animals. This illustrates the valueof the international collaboration and the potential benefits they bring to society.
Specific points(Outstanding points)
The capacity to be prepared when novel agents emerge, and to have the methodologies and trained personnel
available for the control of zoonoses are invaluable programmes to protect society.
(Suggestions for improvement)
In the presentation of their programs it would be beneficial for the staff to emphasize the contributions eachsection of the program is making to global society.

II. Education
Is the educational system and curriculum designed to help develop researchers who possess specialized knowledge
and are capable of working internationally?

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Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons)
One of the really impressive components of the GI-CoRE is the graduate school that trains students from allover the world in the control of zoonoses. This is a prestige program that Hokkaido University can be justifiable
proud of. It fulfills a need for trained personnel that is not met anywhere else in the world. The extent ofinternational collaboration is extremely impressive with students from 32 countries with a special emphasis on
developing countries.
Specific points(Outstanding points)
Nineteen students have already graduated with PhDs-twelve from international countries, and seven fromJapan, again emphasizing the focus on international collaboration. While eight of the graduates have obtained
positions in Japanese universities the majority of students (eight) have obtained positions in foreign universities.
It is notable that the staff of the graduate school comes from international countries (five) with three being
members of the GI-CoRE staff. There are currently thirty-seven PhD students studying for a PhD. In the time thatthe graduate school has been in existence this is a laudatory achievement.
(Suggestions for improvement)
The reviewers had to ask for the details of the graduate school. Since the Graduate School is a major
strongpoint for the program it is suggested that these details are included in future program reports.

III. Establishment of Framework
Are the necessary systems and frameworks being established in order to conduct international cooperative researchand education?
Evaluation Results and Reasons(Your Evaluation Results)
S / A / B / C / D (circle one)
(Reasons and Specific Points)
The framework for establishment of the global collaborative research and education program for conducting
international cooperative research and education has most certainly been established. The written reports, site visitof the facilities, and presentations by the scientists involved establish that the international collaborative program isalready addressing the major zoonotic threats and is providing the infrastructure and training for future threats toboth human and animal health. The framework covers key regions of the world where emerging and re-emerging

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zoonoses appear, and has the flexibility and trained personnel to deal with the zoonotic emergencies. The coverageof current methodologies in genomic analysis in future diagnosis and control is impressive.
(Suggestions for improvement)
While the number of collaborating institutions throughout the world could be extended, this does notnecessarily add to the strength of the program. The framework is in place to deal with the development andmeasures for diagnosis, prevention, and most importantly for the fundamental understanding of the pathogenesis of
emerging zoonoses.

IV. Overall Evaluation
Up to 65% of the threats to human and animal health come from environmental and zoonotic threats. While
the global organizations through the World Health Organization and Food and Agriculture Organization of theUnited Nations/ World Organization for Animal Health recognize the importance of “One Health-One World” there
is still a paucity of organizations that are aimed specifically at the control of zoonoses and the training of personnel.
The Global Institution for Collaborative Research and Education (GI-CoRE) established at Hokkaido University,
Sapporo fills this global need, not only from the detection of such agents throughout the world, but understanding
the methodologies for rapid detection, the understanding of the molecular basis of their pathogenesis, and thedevelopment of anti-microbial agents and vaccines for their control. The GI-CoRE at Hokkaido University fulfills a
global need, and it looks to the future in the establishment of a graduate school for the training of students who will
undertake the research needed for the development of control strategies.
The strength of the Gi-CoRE at Hokkaido University is based on the successful international collaboration ofworld class scientists that provide not only the collaboration in the various fields, but also make their own facilities
available for student and faculty exchange, increasing the strength and breadth of each institution.
The facilities and equipment at the global station for zoonotic control in Hokkaido University are world class,with an emphasis on biosafety and biosecurity, that is essential for research on organisms that are a threat tohumanity. While the facilities at Hokkaido University do not have a BSL4 facility, one such facility is available to
the group in Japan when such facilities are needed.
The productivity and quality of the research is emphasized by the high number of publications, invitations tonational and international meetings, grants and awards that have been achieved since 2014. Hokkaido University
can be justly proud of their GI-CORE, the concept and success of the program should be considered as a flagshipprogram that is too be continued for the future, for it serves both Japan and the entire world.

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38

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Global Station for Zoonosis Control
Global Institution for Collaborative Research and Education (GI-CoRE)
Final Evaluation
External Evaluation Committee Member Name:

Ben Adler.

Choose one of the five Evaluation Ratings options below as explained by the Evaluation Explanation for each
Evaluation Item on the form.
Evaluation

Evaluation Explanation

Ratings
S

Achieved outcomes surpassed the original plan (Outstanding)A

Good progress has been maintained and expected outcomes have been achieved(Excellent)

B

Most expected outcomes have been achieved with some slight delays (Good)C

Although certain outcomes were achieved, overall results were insufficient (Satisfactory)D

No expected outcomes were achieved (Unsatisfactory)

I. Research1.

Has construction of an international research and education center capable of attracting outstanding researchers

from around the world (including from HU) been achieved?
Evaluation Results and Reasons(Your Evaluation Results)
A(Reasons)
Absolutely yes. The Center has clearly attracted world class researchers from HU, from other institutes inJapan, and internationally. With highly regarded researchers from Australia, Ireland, USA and several othercountries, the Center has built a profile such that it is a place to which scientists actively want to come to work andcollaborate with scientists from within Japan and from abroad. It is apparent that the Center has become a nucleus
for workers on zoonotic infections. As such, it is unique in Japan and one of perhaps only a handful of such centersworldwide. After speaking with some of the international collaborators, it was quite evident that the reasons were
twofold, encompassing the scientific reputations of the personnel and the very impressive array of state-of-the-art
equipment and facilities available, or being established, at the Center.
It was equally pleasing to see the level of international collaboration with scientists from many so-called“developing countries”. This is an important initiative, as many of the zoonotic infections under study are the causesof major public health problems in these countries.

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Specific points(Outstanding points)
We especially commend the Director for the initiative of outreach to developing countries.
We also congratulate the Director and his staff on establishing a center with world class equipment andfacilities.
(Suggestions for improvement)
Of course, one should never rest on one’s laurels and there is scope for additional international collaboration
However, in order to not dilute the available resources, such expansions will need to be carefully targeted towards
appropriate zoonotic infections.
2.

Is world-leading cutting-edge international cooperative research underway?

Evaluation Results and Reasons(Your Evaluation Results)
S(Reasons)
Again here, the answer is a very clear yes. We were very impressed with the quality of the science and thepresentations at the Sixth Meeting of the Consortium for the Control of Zoonoses. These ranged from fundamental
research aimed at understanding the mechanisms of pathogenesis of the zoonotic agents under study through totranslational research directed towards the development and/or improvement of vaccines, diagnostic tools and newtreatment regimens. The applied research components are of particular relevance to global regions which may nothave the necessary resources to undertake this development. In this context, the range of over 30 countries involved
can only be described as impressive and remarkable. The fact that approximately 75% of the collaborating countries
are from resource poor regions is commendable.
The publications flowing from the research are excellent, both in terms of numbers and also in terms of
quality. A high proportion of the papers is in highly-ranked discipline-specific journals or in top multidisciplinary
journals. Of course, publications should not be the only criterion used to assess the quality and value of the research.
The applied research within the Center (as is the case worldwide) may not necessarily result in high impact papers,
but the public and social benefit of for example a more accurate diagnostic test or an improved vaccine cannot be
overstated.
Overall therefore, the cooperative research in the Center is viewed as outstanding.
Specific points(Outstanding points)
The spread of basic and applied research
The involvement of a high number of developing countries.
(Suggestions for improvement)

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3.

Are research outcomes from GI-CoRE being actively utilized to solve social issues?

Evaluation Results and Reasons(Your Evaluation Results)
A(Reasons)
The basic ethos of the research in the Center is to solve social issues. Infectious diseases remain a major causeof morbidity and mortality worldwide. At least 70% of these infections have a zoonotic origin. Any research that has
the potential to alleviate this suffering will therefore have very significant social impact. This is especially importantin the current context of the emergence of major problems of resistance of bacterial and parasitic pathogens and theongoing difficulties of specific antiviral therapeutic agents. As such, a component of the research program seeks to
specifically address these issues. This is relevant and appropriate.
Specific points(Outstanding points)
The emphasis on vaccines, diagnostics and therapeutics.
(Suggestions for improvement)
None that could be achieved without a massive increase in funding.

II. Education
Is the educational system and curriculum designed to help develop researchers who possess specialized knowledge
and are capable of working internationally?
Evaluation Results and Reasons(Your Evaluation Results)
S(Reasons)
Absolutely outstanding! The fact that 19 PhD students have already graduated from the Center is a superb
early outcome. Notably, 12 of these were international students, with 10 of them from developing countries.
Members of his latter category are now all employed at universities or institutes outside Japan, commensurate withthe social ethos of appropriate transfer of specialist knowledge within Japan and abroad.
Equally impressive is the number of currently enrolled 37 PhD students. Here again importantly, 21 of theseare from abroad and will be able to contribute expertise locally after graduation.
The establishment of a formal Graduate School of Infectious Diseases is commended and will certainly
enhance the education and training of young researchers.
Specific points(Outstanding points)

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The number, quality and international spread of graduated and current post-graduate students(Suggestions for improvement)
Keep going as you are.

III. Establishment of Framework
Are the necessary systems and frameworks being established in order to conduct international cooperative researchand education?
Evaluation Results and Reasons(Your Evaluation Results)
A(Reasons)
The reasons in terms of high quality research and post-graduate training have been outlined in previous
sections. One additional point warrants mention here. The Center is clearly a major international player in zoonosis
research. This is evidenced by the number of international collaborators and the fact that many researchers come tospend time in the Center, for both short term and long term visits. This will provide a global network of scientists
with expertise in zoonotic diseases. Ongoing mentorship of this network will be critical to maintain and enhance theresearch and education framework.
Specific points(Outstanding points)
The superb facilities available within the Center.
The future international network that will develop from graduating students and visiting staff.
(Suggestions for improvement)
Not really a point for improvement, but rather a comment. It will be important for the Center to establish amechanism to retain contact with the various national and international staff and students after they return to theirown countries or institutions, in order to maintain the network. This could almost be viewed as a network of Center“alumni”.
This could just as easily have received an S. The only reason it has got an A is that there is always room for
improvement.

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IV. Overall Evaluation
We were mightily impressed with what has been achieved so far and encouraged by the future vision of the
Director. The Center has established itself as a major international player which has attracted top quality staff andstudents. The scope of research is quite broad and covers fundamental and translational aspects of zoonosis control.
While this is to be commended, at some future time it may be necessary to prioritise the research focus. We notethat some of the research areas are quite peripheral to the concept of zoonoses.
Overall, we congratulate the Director, staff and students and we recommend unreservedly and enthusiasticallythe continuation of funding for the Center.

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44

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Global Station for Zoonosis Control
Global Institution for Collaborative Research and Education(GI-CoRE)
Hokkaido Univeristy
Research Progress Report(Project Period: Academic Year 2014-2019)45

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Contents
Page

Ⅰ． Overview・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・49

Ⅱ． Budget・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・53

Ⅲ． Detailed Results・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・ 54
1. Research・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・ 56
2. Education (Graduate Schools to Foster Global Human Resources) ・・・・・・・・・・・・・・・・・・126
3. Establishment of Framework ・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・128

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48

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I. Overview■ Name of Global Station (GS)Global Station for Zoonosis Control■ Project Period
2014-2019 academic years (5 years)■ Aims and Goals
The objectives of the Global Station for Zoonosis Control at Hokkaido University are to promote research for thecontrol of zoonoses thorough collaboration with leading international researchers and to establish a collaborative research
network at a global level.
Our major targets, outlined below, are to develop strategies for zoonosis control based on the results of thecollaborative research and to make proposals to the global community.
Our aims are:
1. to reveal the perpetuation mechanisms and transmission routes of zoonotic pathogens by conducting global
epidemiological studies on infectious diseases to improve existing prevention and control strategies.
2. to study the genetics of pathogens and the factors responsible for their pathogenicity and host range.
3. to develop databases of information of the above results and to make freely available to reserachers and the public.
4. to develop and disseminate globally practical measures for the diagnosis, prevention and treatment of zoonoses.
Research subjects
I. Development of Vaccines and Biologicals
I-A Development and practical use of seasonal influenza vaccines of global standard
I-B Transcriptomics in bacterial infection and immunity
I-C Management of influenza virus libraryI-D Development of bacterial vaccines
II. Exploration of Pathogens
II-A Novel virus detection and characterization
II-B Molecular pathogenesis of viral diseases and development of antiviral drugs
II-C Genomic analysis of antimicrobial resistanceIII. Pathogen Genomics
III-A Linking genes to phenotypes in malaria parasites by classical genetics and genomic technologies
III-B Analysis of horizontal gene transfer in protozoan parasite genomes
III-C Development of point-of-care diagnostic systems in resource-poor settings
III-D Additional activities under the framework of GI-CoRE
The GI-CoRE units of each of the participating universities all collaborate to achieve these goals.

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■ Necessity and Urgency
Emerging and re-emerging infectious diseases, for example, influenza, Ebola virus disease, Middle East respiratory
syndrome (MERS), tuberculosis, trypanosomiasis and Zika virus disease, now occur worldwide and have become a major
threat to public health. Most of these diseases are zoonoses caused by agents transmitted from their natural wild animal
hosts, to other animal species, including humans (Figure 1).
Recent rapid changes in the global environment have wreaked havoc on the ecologies of reservoir hosts and led to
expanded opportunities for pathogens to invade human societies. Rapid development of global networks for mass humantravel and food supplies, further exacerbate the problem by providing opportunities for pathogens to spread worldwide
within a short time period. The net result of all these factors is a drastic increase in zoonoses in the 21st century, with thecertainty that even greater numbers of humans will be exposed to infectious diseases in the future, resulting in major
economic and societal costs from the associated morbidity and mortality.
It is obvious from occurrences of zoonoses that even a single outbreak has significant impacts on the global economy
and society. Clearly, control measures that extend beyond national borders are necessary to control these trans-boundary
infectious diseases highlighting the need for the formation of international research networks.

Figure 150

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Control of Zoonoses

Identification of natural host &elucidation of the route of transmission

CONTROL OF ZOONOSES
Development of measuresfor diagnosis andprevention

Clarification of themolecular basis ofpathogenesis
Figure 2

For the control of zoonoses, the rapid identification of natural host animals and their transmission routes is essential.
The technologies to detect microorganisms in nature and the basic research techniques used to determine host ranges,
ecology and pathogenicity, are, however, currently insufficient. Furthermore, there is a lack of expertise and organizations
that conduct and coordinate strategic research for the prediction, prevention and control of zoonoses with the capabilities
to implement control measures into disparate societies around the world.
Recently, the threat to economies and societies has significantly increased due to the emergence and re-emergence oftrans-boundary infectious diseases. As a result, domestic and international demand for development of human resources
capable of conducting infection research and control measures has increased significantly.
Due to these circumstances, the Japanese government formulated “The Basic Policy on Strengthening
Countermeasures for Infectious Diseases that Pose a Threat to Global Society” at the meeting of the Ministerial Council
on the Response to Infectious Diseases held in February 2016. The policy states that in order to confine infectious diseases
at an early stage and, in particular, to prevent infection spreading from a localized epidemic to a pandemic, the developmentof an organization to foster measures to mitigate these threats is an urgent issue.
If a global framework is established that encompasses health governance, basic research activities designed to reveal
the ecology of pathogens and the molecular basis of pathogenicity, in addition to applied research programs to devise new
methods of diagnosis, prophylactic and therapeutic approaches, then it must be conducted at a level which transcends
academic barriers and national borders (Figure 2).

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■ Originality, Novelty, etc.
The Research Center for Zoonosis Control was established in Hokkaido University (HU) in 2005 as an institutespecializing in the promotion of research directed towards the control of zoonoses. In particular, through gatheringresearchers from medical science, veterinary medicine, basic science and information science, the University has created
new opportunities and developed innovative areas of research. Much progress has already been made in the areas of global
surveillance of influenza, the comprehensive search for and discovery of new viruses, the studies of drug-resistanttuberculosis, and the development of rapid diagnostic methodologies. Furthermore, extensive international collaborative
research has been conducted on viral, bacterial and parasitic zoonoses, and a global research network has been established.
As such, the Research Center for Zoonoses Control has become a unique institute in the world.
In December 2010, the Research Center for Zoonosis Control hosted the regional workshop on collaboration between
human and animal health sectors for the prevention and control of zoonoses, in which members from the World HealthOrganization (WHO), the Food and Agriculture Organization of the United Nations (FAO), and the World Organisation for
Animal Health (OIE) gathered together for the first time.
In November 2011, WHO designated the Hokkaido University Research Center for Zoonosis Control as the “WHOCollaborating Centre for Zoonoses Control” up to 2015 and Professor Kida became Head of the WHO Collaborating Centre
for Zoonoses Control. The inauguration ceremony and “the regional forum of collaborating/reference centres on emerging
infectious diseases and zoonoses” were held in December 2011 (Figure 3). In October 2015, WHO re-evaluated andredesignated as a “WHO Collaborating Centre for Zoonoses Control” until November 2019.
In a global context, the project promoted by the Global Station for Zoonosis Control with the Research Center for
Zoonosis Control as a base, has provided an opportunity to attract leading researchers to the University and promotecollaborative international research. The research conducted by each unit leads the world in each field. The four universities
are at the forefront in their fields and the vibrant program of exchange of staff, students and research achievements amongst
the members of GI-CoRE provides a model for others to follow.
Finally, in 2018, Hokkaido University will establish a Graduate School of International Infectious Diseases for thedevelopment of human resources in the fight against infectious diseases. The research activities at the Global Station for
Zoonosis Control will provide the basis for promoting the process of globalization of education and research.

Figure 352

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Ⅱ. Budget
Unit: 1,000 JPY

Budget for
GlobalStation for
Zoonosis
ControlCategory

FY 2014

Personnel cost-

Operating cost-

Facility cost

-

Total

FY 2018

FY 2017(projected)

Total

13,78850,051

92,29245,90845,5399,276

132,91431,36100031,361

5,054

22,68532,29130,94660,000150,976

Administrative
cost*

24,11323,316

20,63018,82624,275111,160

Operating andresearch cost

68,34978,21558,392

57,37333,275

295,604

97,516

202,802

170,640

166,472

176,877

814,307(for researchers fromoverseas)

15,034

FY 2016

13,419Personnel cost

GI-CoRE
establishmentof framework

FY 2015

32,191*Including travel expenses for invited international researchers

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III. Detailed Results● Framework of the Global Station for Zoonosis Control
The current situation with regards to the sharing of roles and cooperation between HU and affiliated universities isshown in Figure 4. The global station comprises three research units, in each of which principal investigators (PIs) areresponsible for research projects as listed in the figure below. Each unit conducts its own research projects independently,
but interactions and collaborations between units are encouraged. To integrate research activity toward the goal of “controlof zoonoses”, we have constructed the “Consortium for the Control of Zoonoses” where all unit members meet together
and exchange information. Consortium meetings are held annually with frequent interactions fostering further collaborative
projects.
The Research Center for Zoonosis Control, HU is responsible for provision of office and laboratory space for thoseinvited from international universities. GI-CoRE members are free to access facilities and equipment such as Biosafety
Level-3 (BSL-3) laboratories, BSL-3 animal facilities, core laboratories where flow cytometry-cell sorting systems, next
generation sequencers, cell imaging systems, ultracentrifuges and other analytical equipment are installed. Support staff forlaboratories and core facilities are also allocated by Hokkaido University.

Figure 4
Role sharing between faculty members at HU: The role sharing between faculty members at HU and affiliateduniversities54

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●Future developments
Currently, a solid structure has been formed to conduct research activities within each unit. Based on GI-CoRE activity,a research network, the “Consortium for the Control of Zoonosis”, has been organized in order to promote collaborations
among the affiliated universities. Once a year, the global station organizes the consortium meeting in order to facilitate
information exchange and more active collaboration among members. We also invite members from institutions(universities, research institutes, companies, etc.) other than the affiliated universities to expand our research network. This
network activity will be expanded toward our goal of developing a structure for a Global Center for Zoonosis Control.

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Detailed Results for the “Unit for the Development of Vaccines and Biologicals”
1. Research
1.1 Goals
As the “Unit for the Development of Vaccines and Biologicals”, University of Melbourne (UM) and HU (ResearchCenter for Zoonosis Control and the Graduate School of Veterinary Medicine) conduct research on the development andpractical use of seasonal influenza vaccines of global standard in collaboration with industries, universities and governmentalorganizations for the preparedness of future pandemic influenza. Vaccines against bacterial diseases, including anthrax, are also
developed. In addition, we analyze mucosal innate immune responses that contribute to pathogen clearance and disease
pathology using mouse infection models of bacterial pathogens.
1.2 Current Progress/Future Developmen
1.2.1

Construction of base

● Role sharing with affiliated universities
Affiliated institutions
University of Melbourne,
Australia
Department of
Immunology andMicrobiology

Hokkaido University, Japan
Research Center for
Zoonosis Control

Researcher nameProfessor David Jackson
Professor Lorena Brown
Asst. Professor Brendon Chua
Asst. Professor Toshiki Sekiya(Based at HU)
Dr. Edin Mifsud
Professor Elizabeth Hartland

 Evaluation of proprietary adjuvants Analysis of immunological and biologicalresponses following administration of
vaccine candidates Development of bacterial vaccines

Professor Hiroshi Kida
Assoc. Professor Masashi Shingai

 Comparison of immunogenicity and safetyof whole virus particle vaccine with split
vaccines
 Route of inoculation of vaccines Pre-clinical and clinical tests
 Revision of the biological standard of
influenza vaccines for human use Development of bacterial vaccines

Professor Hideaki Higashi
Graduate School of
Veterinary Medicine

Description of research

Professor Motohiro Horiuchi
Professor Yoshihiro Sakoda

 Transcriptomics in infection and immunity

 Transcriptome analysis of innate cellmediated immunity in infectious andinflammatory diseases
 Management of influenza virus library Bioinformatic analysis of influenza virus
strains

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In collaboration withProfessor Kazumasa Ogasawara, School of Medicine, Shiga University of Medical Science
Collaborating industries, the member of the All-Japan Influenza Vaccine Study Group:1) Kitasato-Daiichi Sankyo Co. Ltd., 2) Takeda Chemical Industries Co. Ltd., 3) Handai Biken Inc. Fd.,
4) Kaketsuken Inc. Fd., 5) Denka Seiken Co. Ltd.
Kaketsu-ken
KitasatoDaiichi-Sankyo

HU
RCZC

DenkaSeiken

Bilken-kai
TakedaCI

Global standard whole inactivatedseasonal influenza virus particle
vaccine of 100 % purity

All-Japan Influenza Vaccine Study Group

1.2.2

International Collaborative Research● Current progress in meeting initial research goals
Project I-A: Development and practical use of seasonal influenza vaccines of global standard
The current split seasonal influenza virus vaccine was developed in 1972 in Japan. This split vaccine is still used today
due to reduced pyrogenicity and decreased adverse reactions following vaccination. However, the efficacy of split vaccines
is extremely low and, importantly, does not protect high risk groups (infants and the elderly) from severe disease associatedwith influenza virus infection.
Because the immunological potency of the current split vaccine is limited, efforts have been made to enhance
immunogenicity by using the following methods;
1) to annually update the vaccine to protect against the influenza viruses most likely to spread in the upcoming season,
2) to use higher doses (up to four times) of the vaccine which have been approved for people aged 65 and older in the
US and Canada,
3) to apply intradermal administration of vaccine using a much smaller needle than normally used,
4) to use an adjuvanted seasonal influenza vaccine for people 65 years of age and older and vaccines formulated with
MF59 or AS03 (oil-in-water adjuvants) approved in Europe and the US, and5) to use live attenuated nasal-spray vaccines which have been demonstrated to have higher efficacy in children instudies in the US where it has been approved for people from two to 49 years of age.
These are interim measures, and not ideal solutions for effective vaccination for influenza. Therefore, the seasonal
influenza vaccines need to be significantly improved.
Whole virus particle vaccines induce effective immune responses but have the potential to induce adverse reactions
due to the enhanced innate immune response elicited. Therefore, the aim of this study is to compare the immunogenicity ofwhole virus particle vaccines to split vaccines in order to develop the vaccines as the new gold standard for a seasonal
influenza vaccine.
To achieve this purpose, we have established an All-Japan Influenza Vaccine Study Group in which all five influenza

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vaccine manufacturers in Japan have participated since April 2015. The goals of the program are;1) to compare the immunological potency and safety of whole virus particle influenza vaccine to the current split virus
vaccine provided by each company,2) to perform pre-clinical and clinical trials of the test vaccines developed, and
3) to evaluate proprietary adjuvants and the route of vaccine inoculation.
Status of the Study
1) In April 2016, a material transfer agreement was exchanged with each of the participant vaccine producers.
2) Whole virus particle and ether-split vaccines were prepared by each of the All-Japan Influenza Vaccine Study Group
members. Each of the members is assessing the immunological potency, safety and other properties of their own
test vaccine products.
3) HU, Shiga University of Medical Science, and UM teams are analysing the immunological and biological responses
in vitro and in vivo (mice and cynomolgus monkeys) following administration of each of the vaccine candidates.
Subcutaneous administration of whole virus particle vaccine induced significantly higher neutralization titers for
influenza virus in C57BL/6 mice compared with that of split vaccine (Figure 5).
4) HU and UM teams have started to study theeffect of the vaccine inoculation route and theuse of adjuvants on vaccine efficacy.
5) The third to seventh meetings of the All-Japan
Influenza Vaccine Study Group were held in
June 2016, December 2016, March 2017, June2017 and December 2017 and the eighth
meeting of the All-Japan Influenza Vaccine
Study Group will be held on June 8th, 2018.
6) Kaketsuken, as a representative of the All-Japan
Study Group, has prepared prototype vaccines
for pre-clinical study.
7) The All-Japan Study Group has almost finished

Figure 5
Whole virus particle vaccine (WV) diluted up to 10 foldinduced significantly higher neutralization titers for
influenza virus in mice compared with split vaccine (SV).

pre-clinical study and have started priorconsultation to the Pharmaceuticals and Medical Devices Agency (PMDA) based on our pre-clinical study results.
8) Kaketsuken, as a representative of the All-Japan Study Group, is preparing an investigational new vaccine forclinical trials (phase I and II).
Project I-B: Transcriptomics in bacterial infection and immunity
Host innate defense relies on the activation of signaling pathways that regulate inflammation and cell death. The
subversion of these pathways by microbial pathogens is a common step in the pathogenesis of many infections. In this way,
pathogens may manipulate the innate immune response in infected cells. We are using mouse and amoebae infection models
and the pathogens, such as, Legionella pneumophila (L. pneumophila) and Citrobacter rodentium to understand the mucosal

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innate immune responses that contribute to pathogen clearance and also disease pathology.
Status of the Study
These collaborative studies were undertaken using next generation sequencing and data analysis platforms at HU.
1) The aim of this study was to understand the contribution of SnpL, which is one of effector proteins transported tothe host cell nucleus, to Legionella infection and its effect on host cell transcription. This was achieved using astable, inducible macrophage cell line expressing SnpL and RNA sequencing (RNAseq) to identify perturbations
to the transcriptional profile of macrophages. A manuscript describing the function of SnpL is currently in review
at Cellular Microbiology and this data was used to obtain funding from the Australian Research Council (AU$ 414K
over three years), to investigate nuclear localized effector proteins of Legionella. This application included GICoRE as a partner investigator.
2) Infection with L. pneumophila induces massive infiltration of monocyte-derived dendritic cells (moDCs) into thelung. moDCs are an inflammatory dendritic cell type that are not major antigen presenting cells, but little is known
about the signaling pathways, specific transcription factors activated in moDCs and their function during lunginfection. Global transcriptional responses in primary moDCs from lung infection was examined by RNAseq tounderstand the pathways needed to respond to L. pneumophila infection. We identified multiple guanylate binding
proteins (GBPs) that were upregulated in response to interferon gamma. We are currently generating knockout miceby the CRISPR system to determine if GBPs contribute to innate defense against L. pneumophila infection. Thisdata was used to obtain funding from the Australian National Health and Medical Research Council (AU$ 628K
over three years), investigating the role of GBPs in lung defense against L. pneumophila. This application included
GI-CoRE as an associate investigator.
3) We have discovered new pathways and immune cell types that contribute to host defense against Citrobacterrodentium, an enteropathogenic Escherichia coli (EPEC)-like pathogen of mice. Our previous work aimed todissect the contribution of RipK3, Casp8 and RipK1 in protection against acute colitis using double and triple
knockout mice. RNAseq analysis of the pathogen-infected colon tissue from triple knockout mice showed that
expression levels of serum amyloid protein were altered, but this was inconsistent when tested by qRT-PCR. No
other differences in gene expression were observed among knockout mice, suggesting that the susceptibility ofanimals may not result from defects in colonocyte signaling. Continuing work is testing the susceptibility of theknockout mice to other pathogens, such as, Salmonella which is a systemic pathogen.
4) A new project to examine the transcriptional response of amoebae to L. pneumophila infection is under way.
Amoebae serve as the environmental host for L. pneumophila replication, but little is known about amoebae defense
pathways against L. pneumophila infection. We have performed RNAseq on L. pneumophila-infected amoebae atdifferent stages of the life cycle to understand how L. pneumophila leads to amoebae cell death.
Project I-C: Management of influenza virus library
It is now believed that each of the past pandemic influenza viruses is a genetic reassortant generated in a pig between
avian influenza virus and the preceding human strain. We have shown that pigs are susceptible to infection with each ofavian and mammalian influenza viruses of different hemagglutinin (HA) subtypes, generating reassortants with humanreceptor specificity. Since each of the influenza A viruses of all known subtypes perpetuates among migratory ducks and59

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their nesting lake water and avian virusesof any subtype can contribute genes in thegeneration of reassortants in pigs, thus,
none of the combinations of the 16 HA and9 neuraminidase (NA) subtype viruses canbe ruled out as potential candidates for
future pandemic strains. Therefore, global
surveillance of avian, swine and human
influenza and drastic improvement of flu
vaccines are clearly of crucial importancefor the preparedness for forthcoming
pandemics.
Figure 6
Influenza virus library and database

Status of the Study
Since each of the HA genes of past

pandemic virus strains originated from a duck influenza virus that is antigenically and genetically highly stable, we haveestablished a library of more than 3,000 low pathogenic avian influenza virus strains of the 144 possible combinations of
the 16 HA and 9 NA subtypes for vaccine strain candidates and diagnostic usage (Figure 6). Virus stocks and theirinformation including nucleotide sequence for candidate library are now available at HU in preparation for influenza
pandemics (http://virusdb.czc.hokudai.ac.jp).
Project I-D Development of bacterial vaccines
Inhalation anthrax, resulting from exposure to aerosolized spores of Bacillus anthracis (B. anthracis), is a serious
threat to both humans and animals. The toxicity of anthrax is dependent on three proteins; protective antigen (PA 83 , whichbinds to the host cell surface through the anthrax receptor ANTXR2), lethal factor (LF) and edema factor (EF) which
individually are non-toxic. Following removal of a 20 kDa fragment from the N-terminus of PA 83 , the resulting PA 63
associates to form a heptamer which then transports a complex formed between EF and LF to the cytosol of infected cells
resulting in cell death.
Antibodies (Abs) directed against PA have been shown to mediate protection against B. anthracis in animal models of
inhalation anthrax. The protection correlates with the ability of the antibodies to neutralize anthrax lethal toxin (LeTx) in
vitro using a toxin neutralisation assay. Currently licensed vaccines in the US and UK consist of acellular culture filtratesof B. anthracis formulated with aluminium-based adjuvants. These vaccines induce PA-specific neutralising antibody
which underlie their protective efficacy. The extensive immunisation protocol required for the establishment andmaintenance of immunity for B. anthracis and the severity of potential sites of injection motivates the development of a
new generation of anthrax vaccines.
Peptide sequences can be used to represent target epitopes of intact proteins potentially allowing for precise directionof immune responses to that target. Peptide-based vaccine candidates also have the advantages of (i) eliminating thepotential risk of reversion to virulence, (ii) minimisation of the presence of deleterious sequences by judicious selection of
the peptide sequence and (iii) overcoming limited availability of antigens (Ag). Furthermore, because of the methods of

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chemical synthesis that are used in their manufacture, peptides lend themselves conveniently to chemical modification suchas the attachment of carbohydrate antigen, lipid moiety and other biologically active groups, including adjuvants. Following
analyses of the quaternary structures of PA and LF, we selected four peptides from PA and one peptide from LF as target
epitopes for evaluation as vaccine candidates against B. anthracis. The five peptide sequences that we investigated aredescribed as follows:
1) Helix: the peptide sequence 555DQQTSQNIKNQ565 of PA 63 was chosen because it is in a region of PA 63 which is
involved in the association of neighbouring subunits of the PA 63 heptamer. It was reasoned that assembly of the PA 63
heptamer could be prevented by antibodies directed against this helix thereby inhibiting correct formation of thetoxin.
2) Loop1: the peptide sequence 269IILSKNEDQSTQNTDSETRTISK291of PA 63 was chosen because it is in a region of
PA 63 which is involved in contacting the cell surface receptor, ANTXR2. It was reasoned that antibodies directedagainst this region of PA would prevent the attachment of PA to the cell surface receptor thereby inhibiting the toxins
effects.
3) Loop2: the peptide sequence 648DTEGLKE654 derived from PA 63 was chosen for the same reasons as described above
for Loop1.
4) PA 30 : The 30-residue peptide 168STSAGPTVPDRDNDGIPDSLEVEGYTVDVK197 located at the N-terminus of
PA 63 was chosen because we hypothesized that antibody raised against this peptide may stop the furin-like proteasefrom cleaving the first 20 residues peptide to generate the active form of PA 63 .
5) LF679-701: this peptide sequence, 679NDSEGFIHEFGHAVDDYAGYLLDK701is located at the binding site of lethal
factor which binds to the mitogen-activated protein kinase kinase substrate (MAPKK) a region necessary for its
toxicity. We reasoned that antibodies directed to this region of the molecule would contribute to Ab-mediatedinhibitory effects of an anthrax vaccine.
A T helper cell epitope with the sequence ALNNRFQIKGVELKS which is derived from the light chain ofhemagglutinin of influenza virus A was incorporated into all vaccine constructs. This T helper cell epitope has been shown
to be active in BALB/c mice which was used in this study. A TLR2 agonist, 2,3-dipalmitoyl-S-glycerylcysteine (Pam2Cys),
was also incorporated into each of the vaccine constructs as a built-in adjuvant to create self-adjuvanting lipopeptide vaccine
candidates. Each of the vaccine candidates were constructed using a modular approach developed by us (Zeng, W. et al. J.
Biol. Chem. 2011).
Groups of five BALB/c mice were used in animal studies to determine the antibody responses following inoculationof peptide constructs. Each of the lipopeptides, Helix, Loop1, Loop2 and LF679-701 assembled using the modular approachwere administered subcutaneously by tail vein injections in saline. A group of mice also received a mixture of Helix, Loop1,
Loop2 and PA 30 -based lipopeptide constructs. PA30 alone was administered to mice in the presence of Freund’s adjuvant.
Mice were inoculated on days 0 and 21 and sera were prepared from blood taken on Days 21 and 35 and used in an ELISA
to determine the titres of primary and secondary antibody responses. PAD-1 obtained from GI-CoRE at HU andcharacterised to be of a high quality was administered to a group of mice using Freund’s adjuvant to determine its ability
to induce antibody responses.

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Status of the Study

Figure 7
Anti-peptide antibody responses in mouse sera determined by ELISA following inoculation of peptide-based vaccine
constructs. Each of the immunogens was given on two separate occasions on days 0 and 21 and sera prepared fromblood taken on days 21 and 35 were used for determination of the Ab titres against each individual Ag.

Helix-based vaccine construct not only induced a strong antibody response against itself measured by an enzymelinked immunosorbent assay (ELISA), but these antibodies also bound to PA 63 from which its sequence is derived. The
Loop1 peptide-based vaccine candidate induced a strong antibody response against itself but not to PA 63 . The Loop2
peptide-based vaccine did not elicit any significant antibody response against itself or against PA 63 . The lipopeptide basedon LF679-701 induced a strong anti-LF679-701 antibody response following two inoculations of antigen. PA 30 in complete
Freund’s adjuvant administered to mice in three separate doses elicited a high anti-PA 30 antibody titre (Figure 7). The groupof mice which received the mixture of Helix, Loop1, Loop2 and PA 30 lipopeptide constructs in saline elicited a strong antiHelix and anti-PA 30 antibody responses. Anti-Loop1 and anti-Loop2 antibody responses were not determined in thisexperiment. Inoculation of mice with PAD-1 induced strong anti-PAD-1 responses following three injections and also astrong anti-PA 63 antibody response. The anti-sera obtained from inoculation of PA 30 in Freund’s adjuvant and the mixtureof Helix, Loop1, Loop2 and PA 30 lipopeptide constructs in saline also elicited a strong anti-PA 63 antibody response.
An in vitro toxin neutralisation assay was used to assess the ability of the various anti-sera to neutralise toxins. AntiHelix, Loop1 and Loop2 antibody sera showed little or no toxin neutralisation activity in comparison to the anti-PA 63 sera
which was raised against PA 63 and showed a very high toxin neutralisation activity. We also examined the ability of theanti-PA 30 and anti-PAD-1 sera for their abilities to neutralise anthrax toxins. Anti-PA 63 antisera possesses high toxin
neutralisation activity. In contrast, anti-PA 30 and anti-PAD-1 sera demonstrated only slightly higher toxin neutralisation
activity than normal mouse sera.
In this study, we selected five target epitopes from PA and LF based on their crystal structures and successfully
synthesised five lipopeptide vaccine constructs based on these target sequences. Animal studies show that two of theselipopeptide-based vaccines not only induced strong and specific antibody responses against the immunizing antigen but

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also strong antibody responses again intact PA, as determined by ELISA. Although these anti-sera did not perform as wellin the in vitro toxin neutralising assay as the anti-intact PA antibody, nevertheless, the detection of cross-reactive antibody
responses to PA with anti-Helix and anti-PAD-1 is encouraging. Clearly additional studies need to be performed to further
develop the appropriate target epitope(s), including Helix and PAD-1 that will not only will induce strong antibody
responses towards PA or LF but also induce antibodies that can neutralise toxin activity and perform well in an animal
challenge assay. It is possible that by increasing the length of Helix and/or LF679-701, which also possess helical structure
within the native structure, improved vaccine candidates may be obtained. An additional avenue to follow will be toassemble chimeric structures such as Helix-PAD-1 conjugates. A further advantage associated with the lipopeptide
technology described in this study is that these Pam2Cys-based vaccine constructs are self-adjuvanting and can be
successfully delivered intranasally as we have shown previously. This route of inoculation may be more appropriate toestablish an effective defence against inhalation anthrax.

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Detailed Results for the “Unit for Exploration of Pathogens”
1. Research
1.1 Goals
The “Unit for Exploration of Pathogens”, comprising HU (Research Center for Zoonosis Control and Graduate Schoolof Veterinary Medicine), University College Dublin, Ireland and the National Institute of Hygiene and Epidemiology, Hanoi,
Viet Nam conduct surveillance to identify natural animal reservoirs and transmission routes of zoonotic pathogens, and todelineate pathogenicity determinants and the host range of the pathogens. The research outcomes are employed for thedevelopment of diagnostic technologies and therapeutic strategies directed against zoonoses, in collaboration with thepharmaceutical sector. Research is also conducted on bacterial pathogens, with particular reference to genomic analysis
and drug resistance profiling.
Both of HU and University College Dublin also conduct the education and training of young, early-stage researchers
to become qualified “Zoonosis Control Experts” who are responsible for the control of zoonotic diseases worldwide.
1.2

Current Progress/Future Developments

1.2.1

Construction of base

● Role sharing with affiliated universities
Affiliated institutions
National Virus Reference
Laboratory, University College
Dublin, Ireland
Hokkaido University, Japan
Research Center for Zoonosis
ControlGraduate School of Veterinary
Medicine

Department of Immunology andMolecular Biology,
National Institute of Hygieneand Epidemiology, Vietnam

Researcher nameProfessor William W. Hall
Asst. Professor Michael Carr
(Based at Hokkaido University)

Description of research Development and establishment ofinternational collaborative research among
global institutions
 Analysis of pathogenicity of zoonotic
viruses

Professor Hirofumi Sawa
Professor Ayato Takada
Assoc. Professor Noriyuki Isoda

 Conduct surveillance to identify natural
host animals and transmission routes ofzoonotic pathogens
 Development of diagnostic technology andtherapeutic strategy against zoonotic
pathogens Development of point-of-care diagnostic
systems in resource-poor settings(Collaboration with KAUST unit) Molecular basis of antimicrobial resistance Analysis of pathogenicity of zoonotic
pathogens Conduction of surveillance to identify
natural host animals and transmission
routes of zoonotic pathogens
 Conduct surveillance of zoonotic
pathogens using human samples
 Development of point-of-care diagnostic
systems in resource-poor settings(Collaboration with KAUST unit)

Professor Yasuhiko Suzuki
Lecturer Keita Matsuno

Professor Nguyen Thi Lan Anh

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,Main Collaborating research institutes
 School of Veterinary Medicine, University of Zambia, Zambia
 Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Japan
 Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University, Japan Graduate School of Pharmaceutical Science, Tokushima University, Japan
 Laboratory of Organic Chemistry for Drug Development, Center for Research and Education on Drug
Discovery, Faculty of Pharmaceutical Sciences, HU, Japan The Faculty of Veterinary Medicine, Bogor Agricultural University. Indonesia
1.2.2

International Collaborative Research● Current progress in meeting initial research goals
Project II-A: Novel virus detection and characterization
Since fiscal year 2014, the “Unit for Exploration of Pathogens” has undertaken extensive collaborative scientificresearch with domestic and international partners which has led to the discovery of many new mammalian viruses withzoonotic potential. This research greatly improves our understanding of viral diversity and epidemiology and the nature of
species specificity of viruses in mammalian hosts. These findings have been disseminated by publication in international,
peer-reviewed scientific journals and presentation at international conferences. With regards to the epidemiological research
activities, surveillance has been undertaken to identify natural host animals and transmission routes of zoonotic pathogens
in collaboration with academic institutions in foreign countries.
Status of the Study
The human immunodeficiency virus type 1 pandemic arose following cross-species transmission of simian
immunodeficiency viruses (SIVs), which naturally infect African non-human primates (NHPs), and subsequent zoonotic
transfer and then establishment and spread in the human population. Therefore, surveillance of SIVs and discovery of new
SIVs in NHPs is critical to improve the monitoring and attempt to mitigate future cross-species transmission of these agents.
In collaboration with the University of Zambia (UNZA), we have screened African green monkeys (AGMs; Chlorocebusspp.) and baboons (Papio spp.) employing an SIV consensus PCR and detected SIV pol gene fragments in 18.9% (18/95)
from AGMs and 1.9% (2/105) of DNA samples from baboons in genomic DNA obtained from splenic tissue. We haveestablished a replication-competent SIV isolate in different human CD4+ T-cell lines following co-culture in vitro with
AGM peripheral blood mononuclear cells. Whole genome characterization was performed by next-generation sequencingof these isolates which demonstrated this novel SIV (SIVagmMAL-ZMB) was distinct from other known SIV strains and,also, ancestral to vervet monkey SIV. Specific screening assays demonstrated SIVagmMAL-ZMB viral RNA in 3.2% (3/94)
of malbroucks (Chlorocebus cynosuros) collected in Zambia with no positives samples from baboons (0/105; 0%). Our
results improve our understanding of the evolutionary history of SIV in NHPs.
Bats harbor greater numbers of zoonotic viruses than rodents per individual species and often live in large colonies,
which may contribute to pathogen transmission and, by virtue of being the only flying mammalian genus, can disseminate
infectious agents over wide geographical areas. Polyomaviruses (PyVs) are genetically highly stable and are known to behighly host specific in mammalian species with no convincing evidence demonstrating host-switching between mammalian
species. For better understanding of the nature of virus-host specificity in different bat host species, in collaboration with

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UNZA, we have investigated the diversity of PyVs in different Zambian insectivorous and fruit bat species and annotatedten novel PyV genomes. We have identified evidence of recombination in the newly described African PyVs and also inhuman, bat, NHP and other mammalian and avian species of PyV. The recombination events were non-random, with hot
spots encompassing the structural regions encoding the viral capsid proteins with cold spots within the nonstructural generegions (Figure 8). We have proposed that intergene recombination of structural regions between PyVs encompassing thecapsid proteins may have facilitated altered tropism(s) and species-jumping events. Strikingly, we found evidence that two
PyV species in different horseshoe bat hosts (genus Rhinolophus) were 99.9 and 88.8 % identical with each other over theirrespective large T antigen coding sequences and therefore represent the same virus species in different bat hosts. Ourfindings demonstrate that PyVs are capable of host-switching events in horseshoe bats and have implications for zoonotic
transmission involving high-consequence pathogens in this bat host.
In addition, we have identified
novel PyVs from fruit bats inIndonesia in collaboration with theFaculty of Veterinary Medicine,
Bogor Agricultural University, theGorontalo State University and theVeterinary

Investigation

andDiagnostic Center in Indonesia.
Using broad-spectrum PCR-based
assays, we screened PyV DNA
isolated from spleen samples from 82
wild fruit bats captured in Indonesia.
Eightfull-length

PyV

genomesequences were obtained using an
inverse PCR method. A phylogenetic
analysis of eight complete viralgenome sequences showedthat

BatPyVs form two distinct genetic
clusters that are genetically different
from previously described BatPyVs.
One group of BatPyVs is geneticallyrelatedincluding

to

the
human

primate

PyVs,

PyV9

and

trichodysplasia spinulosa-associated
PyV. This study has identified the

Figure 8
Recombination analysis of species of PyV. The horizontal axis shows the
positions adjusted to Rousettus aegyptiacus polyomavirus 1 as a reference
and colour-coding of each panel is shown in the respective legends to theright. Phylogenetic compatibility matrix over the species of PyV. Each cellin the matrix reflects the normalized Robinson–Foulds distance between
two neighbour-joining trees corresponding to the respective regions in the
PyV alignment. The vertical axis corresponds to the positions adjusted to
the genome of Rousettus aegyptiacus polyomavirus 1.

presence of novel PyVs in fruit batsin Indonesia and provides genetic information about these BatPyVs relatedness to human pathogens.
Rotaviruses exert a profound burden of diarrheal disease in children with estimates ranging from 120,000-215,000
deaths per annum; however, despite this the role of zoonotic transfer is poorly studied. We have identified a new strain of66

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group A rotavirus in the intestinal contents of a horseshoe bat in Zambia. Whole genome sequencing revealed that theidentified virus, named RVA/Bat-wt/ZMB/LUS12-14/2012/G3P[3], possessed the genotype constellation G3-P[3]-I3-R2C2-M3-A9-N2-T3-E2-H3. Several genome segments of LUS12-14 were highly similar as those of group A rotaviruses
identified from humans, cows and antelopes, indicating interspecies transmission of rotaviruses between bats and othermammals with possible multiple genomic reassortment events.
In addition, we have screened wild animals for other viruses, such as coronavirus (CoV), herpesvirus and bufavirus,
and identified novel bat CoV genes in Indonesian Moluccan naked-backed fruit bats. Phylogenetic analysis suggested thatthese bat CoVs are related to members of the genus betacoronavirus. We have previously isolated a novel alphaherpesvirus
in fruit bats in Indonesia, and established the presence of viruses belonging to other taxa of the family Herpesviridae. We
screened fruit bat DNA extracts by pan-herpesvirus PCR and discovered 68 sequences of novel gammaherpesvirus,
designated 'megabat gammaherpesvirus' (MgGHV). A phylogenetic analysis of approximately 3.4 kbp of continuous
MgGHV sequences encompassing the glycoprotein B and DNA polymerase genes revealed that the MgGHV sequences are
distinct from those of other previously reported gammaherpesviruses. Further analysis suggested the existence of coinfections of herpesviruses in Indonesian fruit bats. We also performed nested-PCR screening and identified bufavirus from
12 megabats in Indonesia. We have determined the near full genome sequence of a novel megabat-borne bufavirus,
tentatively named megabat bufavirus 1. Phylogenetic analyses showed that megabat bufavirus 1 clustered with known
protoparvoviruses, including human bufavirus but represented a distinct lineage of bufavirus. Our analyses also inferred
phylogenetic relationships among animal-borne bufaviruses recently reported by other studies. It is suggested that megabatbufavirus 1, as the first protoparvovirus discovered from megabats, indicates high genetic divergence of bufaviruses.
We investigated zoonotic orthopoxvirus (OPXV) infection among wild animals in Zambia to assess the geographicaldistribution of OPXV. Serological analysis indicated that rodents (14.7%), shrews (33.3 %) and non-human primates(2.1 %) had antibodies against OPXV, suggesting that wild animals living in rural areas of human habitation in Zambia
have been infected with OPXV.
Shrews are small insectivorous mammals that are distributed worldwide. Similar to rodents, shrews live on the groundand are commonly found near human residences. We investigated the enteric virome of wild shrews captured in Zambia
using a sequence-independent viral metagenomics approach. A large portion of the shrew enteric virome was composed ofinsect viruses, whilst novel viruses including cycloviruses, picornaviruses and picorna-like viruses were also identified.
Several cycloviruses, including variants of human cycloviruses detected in cerebrospinal fluid and stools, were detected inwild shrews at a high prevalence rate. The identified picornavirus was distantly related to human parechovirus, which is
associated with severe neurologic disease, inferring the presence of a new genus in this family. The identified picorna-likeviruses were characterized as different species of calhevirus 1, which was identified previously in human fecal samples.
Complete, or near complete, genome sequences of these novel viruses were determined and then were subjected to further
genetic characterization. This study provides an initial view of the diversity and distinctiveness of the shrew enteric virome
and highlights unique novel viruses related to human feces-associated viruses. Viral metagenomic analysis identified a new
parvovirus genome in the intestinal contents of wild shrews in Zambia. Related viruses were detected in spleen tissues fromwild shrews and non-human primates. Phylogenetic analyses showed that these viruses are related to human bufaviruses,
highlighting the presence and genetic diversity of bufaviruses in wildlife.
Zambia is located in Southern Africa with a favourable climate for vector mosquitoes and the potential for arbovirus
disease epidemics in both human and animal populations. While malaria is recognized as the major mosquito-borne disease67

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in Zambia, human or animal cases of arthropod-borne virus(arbovirus) diseases, including flavi- and alphavirus infections
have not been extensively studied. In order to investigate
arbovirus infections in Zambia, we have carried out
surveillance studies to identify mosquito-borne viruses. So far,
we have collected more than 13,000 female mosquitoes which
are the target for arbovirus screening, as they ingest the bloodof mammals for production of their eggs. We have identified
many novel viruses from collected mosquitoes, including
arboviruses and mosquito-borne viruses. We have recently
described the isolation of a novel West Nile virus frommosquitoes and are examining the pathogenicity of the isolated
virus in vivo (Figure 9).
In summary, our research group have identified more than
40 viruses from wildlife, including more than 20 novel viruses

50 nm

Figure 9
Transmission electron micrograph showing
spherical (∼40-nm diameter) and pleomorphic
particles of the newly isolated West Nile virus
from captured Zambian mosquitoes.

and pathogenic zoonotic viruses, such as WNV frommosquitoes and the results were reported in 24 in the international journals (Transbound Emerg Dis 2018, Virus Res 2018,
J Gen Virol 2017, Sci Rep 2016, Emerg Infect Dis 2015, J Gen Virol 2015, Nat Commun 2014, and so on) in collaboration
with the counterparts in foreign countries. This research activity is important to provide an evidence base to better inform
preemptive measures to mitigate the occurnce of zoonoses. For that purpose, it is necessary to identify the natural animal
hosts carrying potential and known human pathogens and to better elucidate the routes by which the pathogens make thetransition from those animals to other animals, including humans. In the future, we will further expand these
epidemiological research activities in further countries, including Viet Nam, Sierra Leone, Taiwan and other international
partners.
Project II-B: Molecular pathogenesis of viral diseases and development of antiviral drugs
Molecular pathogenesis of viral diseases
For the effective control of zoonoses, it is imperative to investigate the pathomechanisms underlying interactions
between host-infected cells and pathogens. Therefore, we also focus on the interactions of host proteins with pathogenderived pathogens and their impact on various stages of the viral life cycle and pathogenesis. For that purpose, we employ
methods, such as RNA interference to knockdown mRNAs encoding host proteins of interest and examine the efficacy of
infection in those cells. Alternatively, we also perform transcriptome analysis in pathogen-infected cells and control cells.
Status of the Study
We have sought to determine which Rab proteins, which belong to the Ras superfamily and play essential roles inregulating many aspects of vesicular trafficking, are involved in the intracellular trafficking of nascent West Nile virus(WNV) particles. RNA interference (RNAi) analysis revealed that Rab8b plays a role in WNV particle release. We foundthat Rab8 and WNV antigen were colocalized in WNV-infected cells, and that WNV infection enhanced Rab8 expression

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in the cells. In addition, the amount of WNV particles in the supernatant of Rab8b-deficient cells was significantly decreased
compared with that of wild-type cells, and WNV particles accumulated in the recycling endosomes in WNV-infected cells.
These findings suggest that Rab8b is involved in trafficking of WNV particles from recycling endosomes to the plasma
membrane.
Another host protein, valosin-containing protein (VCP) is classified as a member of the type II AAA+ ATPase protein
family. VCP functions in several cellular processes, including protein degradation, membrane fusion, vesicular trafficking
and disassembly of stress granules. Moreover, VCP is considered to play a role in the replication of several viruses, albeit
through different mechanisms. We have investigated the role of VCP in WNV infection by inhibition of endogenous VCP
expression using VCP inhibitors and by siRNA knockdown. We have shown that the inhibition of endogenous VCP
expression significantly inhibited WNV infection. The entry assay revealed that silencing of endogenous VCP caused asignificant reduction in the expression levels of WNV-RNA compared to control siRNA-treated cells. This indicates that
VCP may play a role in early steps, such as, the binding or entry steps of the WNV life cycle. Using WNV virus-likeparticles and a WNV-DNA-based replicon, we demonstrated that perturbation of VCP expression decreased levels of newly
synthesized WNV genomic RNA. These findings suggest that VCP is involved in early steps and during genome replicationof the WNV life cycle.
We have also established new methods to examine the efficacy of virus-infected cells using subviral particles (SVPs)
and viral-like particles (VLPs). SVPs self-assemble and are released from cells transfected with expression plasmids
encoding flavivirus structural proteins. Flavivirus-like particles (VLPs), consisting of flavivirus structural proteins and asubgenomic replicon, can enter cells and cause single-round infections. Neither SVPs nor VLPs possess complete viral
RNA genomes, therefore are replication-incompetent systems; however, they retain the capacity to fuse and bud from target
cells and follow the same maturation process as whole virions. We have developed quantitative methods for the detectionof cellular entry and release of SVPs and VLPs by applying a luciferase complementation assay based on the high affinity
interaction between the split NanoLuc luciferase protein, LgBiT and the small peptide, HiBiT.
We introduced HiBiT into the structural protein of WNV and generated SVPs and VLPs harboring HiBiT (SVP-HiBiTand VLP-HiBiT, respectively). As SVP-HiBiT emitted strong luminescence upon exposure to LgBiT and its substrate, thenascently budded SVP-HiBiT in the supernatant was readily quantified by luminometry. Similarly, the cellular entry of
VLP-HiBiT generated luminescence when VLP-HiBiT was infected into LgBiT-expressing cells. These methods utilizing
SVP-HiBiT and VLP-HiBiT will facilitate research into life cycles of flaviviruses, including WNV.
Rabies virus (RABV) is the causative agent of fatal neurological disease. As with other viruses, cellular attachment is
an initial step in RABV infection. Viral attachment factors are host molecules that facilitate viral adhesion on the cellsurface and enhance infection but do not trigger endocytic entry and membrane fusion of viruses. The glycoprotein (G) of
RABV, the only transmembrane protein of RABV, binds to the entry receptors and plays critical roles during RABV entry.
RABV G also binds various cell membrane components, such as membranous proteins, gangliosides, and lipids. Theseprior studies suggested the existence of the attachment factor(s) that contribute to efficient adhesion of RABV; however,
the molecules that serve as attachment factors for RABV infection are unidentified, and the mechanism of cellular
attachment of RABV remains unclear. RABV uses several host membrane molecules as entry receptors, including the
nicotinic acetylcholine receptor, neural cell adhesion molecule (NCAM), and nerve growth factor receptor p75NTR.
Although characterization of the interaction of RABV with these receptors has facilitated our understanding of RABV
infection, the mechanism of cellular attachment and entry of RABV remained to be elucidated. Heparan sulfate (HS), a

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glycosaminoglycan with a disaccharide repeating unit of glucosamine and uronic acid, is abundant on cellular surfaces as
a component of HS proteoglycans. HS is involved in various biological events through interactions with cytokines, growth
factors, proteases, and membrane proteins. Previous work has shown that HS also binds certain viruses and mediates target
cell infection. Soluble forms of HS and heparin, a highly sulfated HS analog, can neutralize infection with viruses that use
HS for cellular attachment by competitive inhibition for binding of cellular HS to the viruses. HS and heparin have also
been shown to inhibit RABV entry; however, this observation has been explained by the assumption that HS antagonizes
the binding of RABV to the entry receptor NCAM because HS also binds to NCAM. Thus, the tripartite relationshipbetween RABV, HS and NCAM is still unclear.
We investigated the role of cellular HS on RABV infection and examined the interaction between HS and RABV anddemonstrated that cellular HS supports RABV adhesion and subsequent entry into target cells. Enzymatic removal of HS
reduced cellular susceptibility to RABV infection, and heparin, a highly sulfated form of HS, blocked viral adhesion andinfection. Direct binding between RABV glycoprotein and heparin was demonstrated, and this interaction was shown torequire HS N- and 6-O-sulfation (Figure 10). We also revealed that basic amino acids in the ectodomain of RABV G serve
as major determinants for the RABV–HS interaction. Collectively, our study highlights a previously undescribed role of
HS as an attachment factor for RABV infection.

Figure 10
Rabies virus (RABV) was mixed with either heparin or the indicated forms of desulfated heparin and theninoculated to SK-N-SH cells. Cells were stained with anti-RABV N antibody and Hoechst 33342 and counted byimaging cytometry. Relative infectivity was calculated by setting the infectivity of mock-treated RABV to 100%.

Prion diseases are fatal neurodegenerative disorders, which show three types of disease presentation, infectious,
inherited, and sporadic. In each type, these transmissible proteinaceous infectious particles devoid of nucleic acid, termed“prions”, are produced in the central nervous system (CNS). No adaptive immune responses are induced upon prion
infection; however, the innate immune response is activated before the onset of the disease. The activation state of microglia
influences pathophysiology of prion infection; however, the detailed mechanism(s) remain to be clarified. Macrophages,
monocytes, and microglia are immune cells that play a key role in innate immunity. In infectious and inflammatory diseases
and cancers, distinct acute and chronic innate immune responses are evoked which greatly influence the subsequent
pathophysiological processes. Thus, the analysis of innate immune response and pathophysiology appears to contribute not
only to a development of prophylactic and therapeutic interventions of infectious disease agents but also to an improvement70

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of the understanding of and development of treatment modalities in inflammatory diseases and cancers as chronic
inflammation. A higher goal of our research is to clarify the roles and functions of macrophages/monocytes in infectious
and inflammatory diseases to utilize this information in the development of novel prophylactic and therapeutic approaches.
We are now collecting gene expression profiles of microglia employing next generation sequencing as one strategy toprogress our research. We are focusing on analyzing the relationship between the pathophysiology of prion diseases during
neuroinfection and neurodegeneration. Our recent studies have suggested that transplantation of mesenchymal stem cells(MSCs) influences the activation state of microglia in prion-infected mice. Thus in 2017, we have focused on the analysisof the activation state of microglia that were treated with MSCs in vivo and in vitro.
Recently, we reported that autologous transplantation of mouse compact bone-derived MSCs (mCB-MSCs) into prion
Chandler strain-infected mice prolonged the survival of mice. Interestingly, the mCB-MSCs transplantation enhanced
further microglial activation with up-regulation of some of the marker genes for M2-type microglia. In order to elucidate
the mechanism for the control of microglial activation with mCB-MSCs, we analyzed how the pathological niche of priondiseases impacts upon on the activation of mCB-MSCs and the influence of factors produced from mCB-MSCs on
microglial activation. Brain extracts from Chandler strain-infected mice stimulated mCB-MSCs with the up-regulation of
COX-2 gene expression, suggesting that mCB-MCSs can adapt to prion diseases in the brain. When LPS-treated microglia
were incubated with the conditioned media from mCB-MSCs that were treated with brain extracts from prion Chandler
strain-infected mice, the expression of CD68, one of the microglial activation markers, was down-regulated. Additionally,
the expression of IL-1β, a marker for M1-type microglia, was down-regulated, whereas the expression of Arg-1, a marker
for M2-type microglia, was up-regulated. These results suggest that the mCB-MSCs treated with brain extracts from prioninfected mice have the ability to shift the activation state of LPS-treated microglia from an M1-type to an M2-type. However,
unexpectedly, conditioned media from mCB-MSCs treated with brain extracts from mock-infected mice or without brain
extracts also appeared to have the same ability. Similar tendencies, down-regulation of CD68 and IL-1β, but up-regulationof Arg-1, were observed when microglia isolated from the Chandler strain-infected mice were used. These results suggest
that, regardless of their activation state, mCB-MSCs intrinsically secrete factors that shift microglial activation state from
M1 to M2-type. We have already acquired RNA-seq data of those microglial cells and bioinformatics is now under way tofind out any specific properties of microglia polarized to an M1 or M2 activation state.
Development of antiviral drugs
In order to control zoonoses, it is important to establish strategies for chemotherapeutic intervention measures against
zoonotic infectious diseases in outbreak settings. Our research group has strongly collaborated with a pharmaceuticalcompany, Shionogi & Co. Ltd. and the Laboratory of Organic Chemistry for Drug Development, Center for Research and
Education on Drug Discovery, Faculty of Pharmaceutical sciences, HU.
Status of the Study
Rabies remains an invariably fatal neurological disease despite the availability of a preventive vaccination and postexposure prophylaxis that must be immediately administered to the exposed individual before symptom onset. Antivirals
which can inhibit RABV replication are identified through screening of small compounds; however, as RABV infection
does not generate easily discernible cytopathic effects in vitro, cell viability assays may not be feasible to observe antiviral
activity of small compounds against RABV. Therefore, we generated recombinant RABVs (rRABVs) encoding NanoLuc

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luciferase (NanoLuc) to facilitate the screening of small compound libraries. NanoLuc expression was confirmed in singlestep growth cures of virus infection and showed that the rRABVs were capable of viral replication without decrease of
luciferase activity through ten serial passages. Furthermore, the rRABVs were able to quantify the antiviral activity of thenucleoside analogue ribavirin against RABV in vitro. These findings confirm the potential of the rRABV encoding
NanoLuc system to facilitate screening of small compounds to inhibit RABV infection.
It has been reported by our group and others that ribavirin, a guanine nucleoside analog, is a potent inhibitor of RABV
replication in vitro but lacks clinical efficacy in symptomatic rabies infection. Therefore, we attempted to identify potential
ribavirin analogs with superior anti-RABV activity. Antiviral activity and cytotoxicity of the compounds were initially
examined in human neuroblastoma cells. Among the tested compounds, two exhibited a 5- to 27-fold higher anti-RABV
activity than ribavirin. Examination of the anti-RABV mechanisms of action of the compounds using time-of-addition andminigenome assays revealed that they inhibited viral genome replication and transcription. Addition of exogenous
guanosine to RABV-infected cells diminished the antiviral activity of the compounds, suggesting that they are involved in
guanosine triphosphate pool depletion by inhibiting inosine monophosphate dehydrogenase. Taken together, our findings
underline the potency of nucleoside analogs as a class of antiviral compounds for the development of novel agents against
RABV.
Chikungunya

fever(CHIKF)isare-emerging

mosquito-borne zoonosis caused by CHIKV infection. The
major symptoms of CHIKF are an acute febrile illness witharthralgia, myalgia, rash, lymphopenia, thrombocytopenia
and gastrointestinal symptoms. In severe cases of CHIKF,
encephalitis has been reported in neonates and fatal diseasecan occur, although rarely, in both the young and the elderly.
The arthralgia is characterized by severe joint pain and canbecome chronic in significant numbers of patients persistingover years as a rheumatoid-like disorder. This painful,
debilitating arthralgia is a major factor affecting the quality

Figure 11
Chemical structure of an anti-CHIKV candidate,Compound-A, which is effective at nanomolar
concentrations and possesses a benzimidazole
structure.

of life in convalescent CHIKF patients. Outbreaks of CHIKF have occurred worldwide since 2004, in Africa, Asia andNorth, Central and South America. It is thought that one factor in the re-emergence of CHIKF could be related to viralgenome mutations which have resulted in an increased efficiency of viral transmission in different mosquito vectors and/or
possibly an increased virulence in humans. Currently there are no licensed prophylactic vaccines or chemotherapeutic
options available for prevention or treatment. Recently, two vaccine candidates have showed promising results in phase I
clinical studies; however, the development of antiviral therapeutics is still in early development. Several studies havesuggested that the development of chronic arthralgia may be related to the severity of the symptoms during the acute phase.
Therefore, effective antiviral treatment during the acute phase could potentially reduce symptoms not only in the acute but
also the chronic phases to diminish the rheumatoid-like sequelae. Recently, several candidates which can inhibit
chikungunya virus (CHIKV) infection have been reported; however, the basis of their inhibitory effects have not been fully
elucidated. We have identified an anti-CHIKV candidate which is effective at nanomolar concentrations and designated as
Compound-A (Figure 11). Using whole genome sequencing of resistant clones, reverse genetics and CHIKV replicons, the72

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viral target region was identified in the nsP4 and the anti-CHIKV candidate inhibits the RNA-dependent RNA-polymerase
function of CHIKV.
Ebolaviruses and Marburgviruses are members of the family Filoviridae. These filoviruses are known to cause severe
hemorrhagic fever in humans and nonhuman primates. There are no commercially available vaccines or therapeutics forviral hemorrhagic fevers, including Ebolavirus disease (EVD) and Marburgvirus disease (MVD). Although it has beenreported that some antiviral drugs such as nucleotide analogues (e.g. T705), which are approved for clinical use for otherviral diseases may also be beneficial against EVD, their efficacies in humans have not been definitively established, andconcerns about adverse effects remain. Thus, the development of effective and safe therapeutics against EVD is of crucial
importance. Using biological assays to analyze filovirus protein functions, we screen chemical compounds in this study,
focusing on each replication step of filovirus infection.
Using vesicular stomatitis viruses pseudotyped with filovirus glycoproteins (GPs), we have previously obtained a leadcompound that inhibits entry of filoviruses into target cells. This compound was further analyzed for structure-activity
correlation with 77 newly synthesized derivatives and we have obtained two derivatives (derivative A and B) that showenhanced ability to reduce infectivity of pseudotyped viruses. We confirmed that derivative B efficiently reduced focus
formation of all filoviruses tested. Anti-viral activity was also confirmed by demonstrating significantly reduced cytopathic
effects of Vero E6 cells infected with these filoviruses in the presence of derivative B. Animal experiments and further
characterization (i.e. pathomechanisms) of the compound are now ongoing. New chemical compound libraries will bescreened soon, focusing on inhibition of viral RNA replication and budding of viral particles.
Project II-C: Genomic analysis of antimicrobial resistance (AMR)
Drug resistance in Mycobacterium tuberculosis (M. tuberculosis)
Our group have been collaborating with researchers in Zambia, Sri Lanka, Nepal, Bangladesh, Myanmar, Thailand,
the Philippines and China on the prevalence of drug resistance in Mycobacterium tuberculosis (M. tuberculosis) clinicalisolates in these countries in order to obtain the basic data useful for the development of rapid, simple and low-cost drug
susceptibility test kits. Our group has elucidated the genetic mutations conferring rifampicin, isoniazid, streptomycin,
pyrazinamide and levofloxacin resistance. In addition, our group has clarified that the tubercle bacillus with a specificgenotype tended to more easily acquire a multidrug-resistant phenotype. However, drug-resistance associated mutations in
specific genes were not found in 5 to 30 % of drug-resistant isolates during our international study. Based on this finding,it presented an opportunity to discover unidentified mutations conferring drug-resistance in M. tuberculosis clinical isolates
which will be essential for the development of rapid, simple and low-cost drug susceptibility test kits. Hence, the goals of
this research study are as follows:
1) To continue the elucidation of drug-resistance associated mutations in specific genes by using polymerase chain
reaction and conventional Sanger DNA sequencing to identify M. tuberculosis clinical isolates without any
previously described mutation(s) in the known drug-resistance associated genes.
2) To identify the mutations that correlate with drug resistance among M. tuberculosis clinical isolates without any
mutation in the known drug-resistance associated genes by using next generation sequencing (NGS) technologies.
3) To establish rapid, simple and low-cost drug susceptibility test kits by combining the data from conventional Sanger
DNA sequencing and NGS analyses.

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4) To evaluate the established drug susceptibility test kits in Zambia, Nepal and Thailand to validate for the rapid
detection of drug-resistance mutations in M. tuberculosis.
Status of the StudyTo

determinepyarazinamide

(PZA)

the

frequency

resistance

and

of
its

correlation with mutation in pncA in M.
tuberculosis clinical isolated from patients in
Lusaka, Zambia, BACTEC MGIT M960 wasused for phenotypic PZA susceptibility testing
while sequencing was used to determine
resistance-conferring mutations in the pncA. Of
all the 134 isolates analyzed, 33 were
phenotypically resistant to PZA. Among
multidrug-resistant M. tuberculosis (MDRMTB) isolates, the frequency of PZA resistancewas 22 of 38 (Table 1). And 28 of 33 PZA resistant isolates had mutations in the pncA that confer resistance. With BACTEC
MGIT 960 as the reference standard, gene sequencing showed 84.8% sensitivity and 100% specificity (Table 2). Nine new
mutations were identified and the single nucleotide substitution T104G and C195T were the most frequent mutations.
However, they were observed
in

both

susceptible

andresistant strains indicatingthat they are non-resistanceconferring mutations.
It has been demonstrated
that

PZA

susceptibility

testing is necessary, especially in patients infected with MDR-M. tuberculosis, as approximately half of the bacilli have
PZA-resistant TB. Similar studies are required in other provinces to get a more accurate estimate of PZA resistance inZambia. Mutations in pncA were the major mechanism of PZA resistance; however, the presence of mutations among
phenotypically PZA-susceptible M. tuberculosis isolates makes it challenging to independently use genotyping methods
for the determination of PZA resistance.
Characteristics of MDR-MTB clinical isolates in Nepal and Myanmar were also analyzed. In Nepal, the major lineageof circulating MTB was the Central Asian Strain (CAS); however, the Beijing genotype lineage was more prevalent among
MDR-MTB. This year, we focused on the analysis of the CAS lineage of MDR-MTB. A total of 145 MDR CAS isolates
collected in Nepal from 2008 to 2013 were characterized by spoligotyping, employing mycobacterial interspersed repetitive
unit-variable number tandem repeat (MIRU-VNTR) analysis and drug resistance-associated gene sequencing.
Spoligotyping analysis showed that the CAS1_Delhi SIT26 predominanted (60/145, 41.4%). By combining spoligotyping
and MIRU-VNTR typing, 145 isolates were discriminated into 116 different types including 18 clusters with 47 isolates(clustering rate: 32.4%). About 50% of these isolate clusters shared the same genetic and geographical characteristics with74

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other isolates in each cluster. Some of them shared rare point mutations in rpoB, likely associated with rifampicin resistance,
including a 3-codon deletion and amino acid substitution events, such as, double mutations like Asp516Phe (GAC→TTC)
and Ser531Gln (TCG→CAG). The observed high diversity of the MDR CAS isolates in Nepal suggested the bacteria
progressively acquired drug resistance and became MDR in each patient in the majority of the cases, although some cases
were suggested to be possible transmissions of MDR-MTB. In Myanmar, the major lineage of circulating MTB was IndoOceanic lineage, but the Beijing lineage predominanted among MDR-MTB. A total of 212 MDR Beijing clinical isolates
collected in Myanmar in 2010 and 2012 were characterized as a retrospective study by the same methodologies describedabove. MIRU-VNTR analysis differentiated the 212 isolates into 143 patterns including 37 clusters comprising 110 isolates.
The number of isolates in a cluster ranged from 2 to 8 and most of the clusters consisted of less than 3 isolates. However,some of the isolates shared unique mutations, which were likely associated with rifampicin or isoniazid resistance, including
mutations observed in rpoC suggesting the bacteria had recovered the enzyme function by acquiring the compensatory
mutation. The high genetic diversity of isolates suggested a reduced likelihood of MDR-MTB outbreaks; however, thetransmission of MDR-MTB was indicated in some instances, as was observed in the analysis of the Nepalese cases.
Drug resistant potential in Enterobacteriaceae
AMR is one of the major concerns in public health at a global level. In Thailand, we have isolated numerous
Escherichia coli (E. coli) and Salmonella from both pig and pork showing drug resistant potential. Genes responsible fordrug resistance and plasmid(s) encoding the resistant gene(s) should be detected to better understand plasmid-mediatedtransfer of drug-resistant potentials between Enterobacteriaceae. By comparing the plasmids conferring drug resistantpotential among two Enterobacteriaceae but in identical individuals, we can elucidate the horizontal gene transfer of drug
resistant potential between bacterial species. This project is a collaboration with Thammasat University, Thailand.
Status of the Study
A total of 120 samples including 60 fecal and 60 carcass swabs were collected in 3 slaughterhouses in Pathurnthani
province, Thailand. A total of 67 samples, including retailed pork and cutting board samples, were collected in 2 markets
in Pathurnthani province. All samples were tested to attempt to isolate E. coli and Salmonella by microbiological procedures
following standard protocols established by the USFDA. Approximately, 10 isolates of suspected E. coli and suspected
Salmonella per sample were collected for further biochemical identification. In slaughterhouses, 1,085 suspected E. coli
isolates and 374 suspected Salmonella isolates were biochemically identified. The proportion of identified E. coli and
Salmonella-positive isolates from 3 slaughterhouses were 76.9% (834/1085) and 93.1% (348/374), respectively. In markets,
610 suspected E. coli isolates and 193 suspected Salmonella isolates were biochemically identified. The frequency ofidentified E. coli and Salmonella-positive isolates from 2 markets were 74.9% (467/610) and 87.1% (168/193), respectively.
In slaughterhouses (A, B and C), a total of 120 tested samples (feces and carcass) were contaminated with E. coli in
100% (120/120) and Salmonella in 64.2% (77/120) of cases; and of 60 swine fecal samples, the detection rates of E. coliand Salmonella were 100% (60/60) and 53.3% (32/60), respectively. Among 60 carcass swab samples, the detection ratesof E. coli were in 100% (60/60) and that of Salmonella were 75.0% (45/60). At slaughterhouse C, fecal and carcass swab
samples were positive for Salmonella in lower percentages than those in slaughterhouse A and B. Overall, the detection
rates of Salmonella isolates contaminated in carcass swab samples were significantly higher than those in fecal samples (p< 0.05). In markets, a total of 67 tested samples were contaminated with E. coli in 100% of cases and Salmonella was75

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detected in 94.0% of samples (63/67). Of pork samples, the detection rates of E. coli were 100% (43/43), whereas those of
Salmonella were 93.0% (40/43). Of 24 cutting board swab samples, the detection rates of E. coli were 100% (24/24),
whereas those of Salmonella were 96.8% (23/24). These results indicated that the detection rates of Salmonella
contamination from pork and cutting board swab samples were comparably high percentages. One likely conclusion is thatthe cutting board is the source of Salmonella contamination in the fresh market. In the future, for E. coli isolates,
pathogenicity-associated genes will be characterized to enumerate the proportion of pathogenic E. coli among the isolates.
For Salmonella isolates, serotyping will be conducted by the WHO National Salmonella and Shigella Center Laboratory(NSSC), Nonthaburi, Thailand. In parallel, each of the isolates will be phenotypically and genetically investigated for their
AMR potential against a total of 8 of antibiotic families. Both E. coli and Salmonella isolated from the same feces or pork
sample will be characterised to find the phenotypic associations in the drug-resistant potential between these two bacteria,
and then determine the correlation of the genes encoding the same drug resistant potential onto the plasmids in two bacteria.

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Detailed Results for the “Unit for Pathogen genomics”
1. Research
1.1 Goals
As the “Unit for Pathogen Genomics”, King Abdullah University of Science and Technology and Hokkaido University(Research Center for Zoonosis Control) conduct researches on zoonotic pathogens from a genomics perspective. The
outcomes of the research are used for the development of diagnostic technologies and therapeutic strategies directed against
the zoonosis caused by protozoan parasites.
1.2

Current Progress/Future Developments

1.2.1

Construction of base

● Role sharing with affiliated universities
Affiliated institutions

Researcher nameKing Abdullah University of Professor Arnab Pain
Science and Technology, Saudi Assistant Professor Axel Martinelli(Based at Hokkaido University)
ArabiaHokkaido University, Japan
Research Center for Zoonosis Professor Chihiro SugimotoControl
Professor Kimihito Ito
Assoc. Professor Junya Yamagishi
Assoc. Professor Manabu Igarashi
Assoc. Professor Chie Nakajima

Description of research Linking genes to phenotypes inmalaria parasites by classical genetics
and genomic technologies

 Analysis of horizontal gene transfer
in protozoan parasites and theirvectors
 Development of point-of-carediagnostic systems in resource-poor
settings (Collaboration with UCD
unit)

Other Collaborators
Assoc. Professor Richard Culleton, Malaria Unit, Institute of Tropical Medicine, Nagasaki University
Dr. Sisira Pathirana, Department of Parasitology, University of Colombo, Sri Lanka
Assoc. Professor Takashi Abe, Institute of Science and Technology, Niigata University, Japan

1.2.2

International Collaborative Research● Current progress in meeting initial research goals
Project III-A: Linking genes to phenotypes in malaria parasites by classical genetics and genomic technologies
Malaria kills almost a million children every year. Despite significant financial investment and decades of research,
we have no effective vaccine, and the drugs and anti-mosquito measures that are relied upon for control are failing. Recently,
there have been reports that the malaria parasite is developing resistance against artemisinin, which is the most effective
drug currently available. If resistance to this drug continues to emerge, and spread, it is conceivable that the burden of77

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malaria, currently intolerable, will increase further. Given this situation, new strategies to control the malaria parasite areurgently required. Of the six species of Plasmodium parasites that cause disease in humans, Plasmodium vivax (P. vivax)
is the most widespread, and causes the highest burden of disease outside of tropical Africa. Despite this, there is currently
very little P. vivax-specific vaccine research ongoing. Furthermore, malaria parasite species closely related to P. vivax, butparasitic on macaque monkeys have recently been observed infecting humans in areas of Southeast Asia [Plasmodium
knowlesi (P. knowlesi) and Plasmodium cynomolgi (P. cynomolgi)], raising the spectre of zoonotic malaria. In recent years,
with the spectacular advance in high-throughput genomic technologies, there is an increased opportunity to combine
modern genomic technologies with classical genetics and bioinformatics-driven approaches to study biology of the parasitewith a focus to look for candidate malaria vaccines in a genome-wide manner. It is now possible to apply classical geneticcross experiments in malaria parasites with distinct phenotypes (e.g. differences in drug susceptibility, antigenicity, growthrate, relapsing behaviour etc.) and undertake a holistic approach by applying deep sequencing and statistical algorithms toidentify genes for a given phenotype within a short period of time in genome-wide screens.
P. cynomolgi is one of the most closely related simian malaria species to P. vivax and has been used to model various
aspects of human malaria, such as protective immunity and relapse. Furthermore, its zoonotic potential makes it medically
relevant. The existence of protocols for genetic manipulation also makes it an ideal model for follow-up studies. One of theobjectives of the proposed work is thus to identify genes for the target antigens of “strain”-specific protective immunity
against blood and liver stage parasites of P. cynomolgi, using the Old World toque monkeys (Macaca sinica) as a model
host. This is expected to identify genes that are targets for immunity and provide vaccine candidate proteins that will beeffective against P. cynomolgi, and very likely against P. vivax and P. knowlesi. As a parallel and complimentary approach,
we will establish in vitro cultures of Plasmodium falciparum (P. falciparum) and potentially P. cynomolgi in HU. The
former will be used to perform in vitro selection of an available cross for in vitro growth rate and adaptation, chloroquine
resistance and polyclonal-antibody immune mediated selection. The purpose of these experiments will be to apply the
Linkage Group Selection (LGS) approach to P. falciparum in vitro for the first time and explore the nature of strain-specificimmunity (SSI) in the most devastating human malaria parasite. These sets of in vitro and in vivo experiments will examine
the viability of artificial genetic crosses in P. cynomolgi and, also, in in vitro cultures for LGS studies and partially remove
the need for a vertebrate host, which will greatly facilitate future experiments with human and simian malaria parasites.
Adapting P. cynomolgi parasites to in vitro cultures with human blood will both facilitate future transfection studies withthe species (e.g. using the CRISPR-CAS system) and also allow us to study adaptation of a zoonotic species to infections
in human hosts.
Status of the Study
Current efforts have been focused on establishing the facilities for the experimental work at HU while a pilot
experimental cross in P. cynomolgi is being tried at the University of Colombo. This included establishing the necessary
facilities for housing and maintaining mosquito colonies, obtaining relevant parasite strains, obtaining the necessary permits
for experimental work with primates, malaria parasites and mosquitoes and hiring an experienced researcher for the in vitro
and animal work.
▪P. falciparum: HB3 genome assembly and in vitro application of LGS
LGS has been widely applied in vivo in both rodent models of malaria and against the human parasite P. falciparum.

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However, thus far, there have been no test of its effectiveness in vitro. In order to test that, a pre-existing cross between two
strains of P. falciparum (HB3x3D7) was grown in vitro and exposed to the antimalarial drug pyrimethamine (PYR). While
HB3 is PYR resistant, 3D7 is susceptible. The mutation underlying PYR resistance in HB3 [S108A in the dihydrofolate
reductase gene (DHFR) on chromosome 4] is well documented. The experiment thus aimed at identifying a corresponding
signature of selection (referred to as a “selection valley”) in a locus containing the DHFR gene on chromosome 4. As partof the experiment, the de novo assembly of the HB3 genome based on a combination of long PacBio and Oxford Nanopore
Technologies (ONT) reads was performed. This produced a more consolidated assembly than the one currently available(50 vs 1194 scaffolds) and allowed a better filtering of the single nucleotide polymorphisms (SNPs) used as quantitative
markers for the experiment. The final outcome shows the presence of a single significant selection valley against thesensitive 3D7 alleles on chromosome 4. The locus encompasses the DHFR gene, thus validating the application of the LGS
methodology in vitro in malaria. This result is relevant for future plans to produce novel crosses of human malaria parasites
using humanised mice to identify loci associated with antimalaria resistance in the field.
▪Sequencing of P. cynomolgi genomes
Three strains of P. cynomolgi have been selected for the production of crosses in monkeys to study the relapse and SSI
phenotypes in malaria. Relapses in malaria are due to the formation of a dormant stage (the hypnozoite) in the liver of thehost, whose genetic basis is still unknown. During a collaboration with Prof. Pathirana in Sri Lanka, a strain of P. cynomolgi(which normally forms hypnozoites) that had never been observed inducing relapses was described. DNA from these strains,
as well as that of two sporozoite-inducing strains was obtained and sequenced by Illumina technology. As part of an effort
to assemble the genome and provide a complete picture of both the SNPs as well as more complex structural variations,work is currently underway to apply selective whole genome amplification (sWGA) to the DNA of the parasites to provide
enough material for the production of long sequence reads by PacBio and/or ONT sequencing. sWGA has been successfully
applied previously to various malaria species present at low quantities in host blood (as is the case with P. cynomolgi) to
produce enough template for whole genome sequencing (WGS). By repeating the same procedure in P. cynomolgi for the
first time, the goal is to produce reference genomes for each of the strains for further studies.
▪Sequencing and assembly of a zoonotic Plasmodium simium (P. simium) genome
P. simium is a monkey parasite closely related to the human parasite P. vivax and found exclusively in South America.
In fact, P. simium is thought to represent a case of anthroponosis of P. vivax from humans to monkeys. Recently, the caseof a human infection with P. simium was reported from Brazil. A genome sequencing and assembly project of this zoonotic
case of infection was started as a collaboration between KAUST in Saudi Arabia and the GI-CoRE within HU. Since noreference genome assembly of P. simium is currently available, this represents the first time such a genome will besequenced, assembled and analysed. An initial assembly split into 2184 scaffolds based solely on short Illumina reads wasproduced and combined into 14 composite chromosomes by synteny with P. vivax, and efforts are currently underway toapply sWGA to produce enough DNA for long read sequencing. This should further consolidate the assembly into larger
scaffolds and remove current gaps. The assembly will then be annotated and compared with the human P. vivax genome toboth confirm its origin as an anthroponosis and to identify key mutations involved in host switching.

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Project III-B: Analysis on horizontal gene transfer (HGT) in protozoan parasite genomes
Apicomplexan parasites exhibit a wide range of biological diversities. The free-living photosynthetic algae Chromera,
which is the ancestor of apicomplexans, has evolved toward the parasitic life style by acquiring infectivity to nonvertebrates, and eventually to vertebrates. One of the crucial steps in the evolutionary path of apicomplexans is adaptation
to arthropods which serve as vectors for the transmission between vertebrate hosts. Parasites utilize arthropods not only ascompartments for the development and vehicles in transmission, but also as partners to exchange genetic material.
Horizontal gene transmission (HGT) is a well-studied phenomenon amongst bacteria; however, it sometime occurs
beyond the kingdoms of Archae- and Eubacteria. HGT often results in "gain-of-function" of the organism that has acquired
the genetic material. The recent report of HGT from mammals to ticks which facilitates the blood-suckling process is agood example of the significance of HGT in the host-adaptation of arthropods. Therefore, HGT is considered to be one ofimportant driving forces in the evolution and acquisition of novel traits.
We are now trying to detect HGT in apicomplexan parasites and their vectors by a genome-wide approach (Figure 12).
Traditionally, evidence of HGT have been detected through conventional tools, such as BLAST and phylogenomics.

Oncecandidate HGT genes are found, homologous genes are identified by the BLAST and phylogenetic searches. However, thisapproach may be not so efficient to detect evidence of HGT in a genome-wide manner. In addition, in the case that theorigins of the HGT are unknown organisms for which DNA sequences have not been well characterized, the conventional
homology-based approaches have fundamental limits. For this purpose, Batch Learning Self-Organizing Mapping

Figure 12
Principal of BLSOM and detection of the evidence of HGT in apicomplexan parasites and their vectors by agenome-wide approach.

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(BLSOM), developed by Dr. T. Abe (Niigata University), can effectively find hidden signatures in genome sequences oftarget organisms based on oligonucleotide composition. This alignment-free clustering method which has been successfully
applied for phylogenetic classification of bacterial populations and arthropods is a very powerful tool to find evidence of
HGT in parasite and vector genomes. We expect that our approach can provide insights into the evolution of interactions
between parasites and their vector arthropods.
Status of the Study
In order to evaluate clustering capacity of BLSOM, we obtained complete genome sequences of arthropods from 11
genera and 34 species, including tsetse fly (Glossina morsitans), protozoan parasites from 23 genera present in genome
databases and analyzed by BLSOM. The sequences from the genome of Glossina clustered into a single node while several
sequences were separated from this cluster. These non-clustering sequences were mapped on the bacterial genus level,
which are therefore presumed to be of bacterial origins. These presumptive sequences included those from Wolbachia,
endosymbionts in insects, Rickettsia, potential animal pathogens, and several other bacterial genera. To validate theaccuracy of the BLOSM HGT predictions, the sequences presumably derived from Wolbachia were used as query sequencesfor BLAST (Figure 13). From a total of 38 sequences, 36 hit to known Wolbachia sequences in the gene database, resulting
in an accuracy of 94.7 %. Genus level BLSOM maps have also been constructed by using genome sequence data from
Plasmodium, Toxoplasma, Trypanosoma, and other protozoan genera. BLSOM analysis gave clear discrimination for eachof the genera. In addition, mapping patterns by BLOSM are in good agreement with phylogenetic relationships analyzed
by conventional homology-based analyses such as BLAST and Clustal Omega. From the clustering profiles, we could
identify evidence of putative HGT between distant organisms, such as HGT between protozoans. Evidence of HGT inprotozoan genomes from prokaryotes are also being analysed. In order to provide evidence that HGT has occurred during
the course of parasite/vector evolution, further analyses are needed.

Figure 13
Schematic summary of potential HGT observed in tsetse fly genome.

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1) Possibility of contamination of bacterial genomic DNA in the materials used for genome sequencing forparasites/vectors should be excluded. This can be done by analyzing flanking genome sequences ofputative HGT regions.
2) Functional analysis of the genes obtained by HGT should be carried out. Coding regions in putative HGT regions
should be determined and annotated. Possible role of the horizontally-acquired genes in metabolic pathways,
parasitism and other biological activities will be analyzed. We also envisage undertaking gene knock out/down
experiments in the target parasites/vectors in order to determine the biological significance of HGT.
Project III-C: Development of point-of-care diagnostic systems in resource-poor settings
Loop-mediated isothermal amplification (LAMP) is a rapid and sensitive tool used for the diagnosis of a variety of
infectious diseases. One of the advantages of this method over polymerase chain reaction is that DNA amplification occurs
at a constant temperature, usually between 60–65°C; therefore, expensive devices such as thermal cyclers are unnecessary
for this step. However, LAMP still requires complicated sample preparation steps and a well-equipped laboratory to produce
reliable and reproducible results, which limits its use in resource-poor settings in most developing countries.
Status of the Study
We have made several substantial modifications to the technique to carry out diagnosis at epidemiological hot spots
or at point-of-care facilities for human African Trypanosomiasis (HAT). One of the improvements is that the LAMP reagentsare air-dried in a single tube so that the activity can be retained for over 6 months at ambient temperatures. This ready-touse LAMP provides an ideal diagnostic system in resource-poor settings and is now currently being tested at clinicallaboratories in Zambia and Malawi as a point-of-care methodology. We are now also introducing a portable sequencing
system for point-of-care diagnosis of various infectious diseases including HAT, dengue fever and chikungunya fever. The
recent invention of a portable sequencer, “MinION” has drastically changed the way DNA sequencing outside specializedlaboratories. MinION has been successfully miniaturized in the form of a portable, one-time use as a universal serial bus(USB) device connected to a laptop personal computer (PC) at a reasonable cost that covers both the device itself as wellFigure 14
Schematic summary of point-of-care diagnostic systems based on LAMP-MinION system.

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as consumables. Conversion of a sample to a sequencing template is also simple, consisting solely of adaptor ligation underisothermal conditions, which can be completed within 1-2 hours. One of the major advantages of the MinION sequencer
lies in the fact that it does not require any installation of conventional laboratory equipment or the use of specific skills inmolecular biological techniques in its sequencing procedure. These features of MinION in combination with LAMP haveopened the opportunity to enable precise genotyping of pathogens in tropical diseases in rural hospitals or in field
circumstances. In order to accommodate demand for the dried reagents, we have set up a small-scale factory with a semiautomated system by using an ink-jet printer at the Research Center for Zoonosis Control, HU. Reagents prepared by thissystem are now provided to the University of Zambia and the University Teaching Hospitals, Zambia and used for clinicaldiagnoses of HAT.
With the combination of MinION with isothermal amplification of viral RNA, we were able to amplify and sequencetarget viral genomes in a single day. The analysis of blood samples collected from 141 Indonesian patients demonstrated
that this method enables the clinical identification and serotyping of the dengue virus with both high sensitivity andspecificity. Similar analyses were conducted on 80 Vietnamese and 12 Thai samples with comparable performancestandards. Based on the obtained sequence information, we have demonstrated that this approach is able to produce
indispensable information for etiologically analyzing annual or regional diversifications of the pathogens (Figure 14, page35). A pilot study of the clinical use of the LAMP-MinION system is also underway at the National Institute of Hygieneand Epidemiology (NIHE), Vietnam in collaboration with Prof. William Hall (University College Dublin). The MinION
sequencing costs $500 per run; thus, it is affordable though still expensive for clinical use. To reduce the cost-per-test, we
examined multiplex sequencing runs with indexed primers. We designed 9 indexes in the loop region of the forward innerprimers and performed the LAMP assay with plasma obtained from patients. In total, we tested 72 plasma by LAMP and
18 amplicons were selected and MinION sequencing performed in duplicate. More than 20,000 primary reads weresuccessfully obtained from each run and they were uploaded and a base calling process was conducted. Our approach isable to produce indispensable information for etiologically analyzing annual or regional diversifications of the pathogens.
Project III-D Additional activities under the framework of GI-CoRE▪Effects of the Pam2Cys adjuvant molecule on malaria parasites
Pam2Cys is a powerful vaccine adjuvant that has been previously shown to modulate strong immune responses in test
subjects. Previous test has indicated that when provided as a preventive treatment it can inhibit the liver stage of malaria
parasites of the rodent model Plasmodium yoelii. In an effort to understand both the antimalarial activity of Pam2Cys andpossible countermeasures adopted by surviving parasites, the transcriptome of parasites emerging from the liver after
Pam2Cys treatment was compared with that of control infections. Results have shown an inhibition of parasite transcription
factors and of the expression of surface antigens, which suggests epigenetic adaptations to the selection pressures imposedby a stimulated immune system (Figure 15). Intriguingly, the pattern of transcriptional inhibition are remarkably similar to
those recently observed in the transcriptomes of parasites, inducing severe malaria. This indicates that Pam2Cys may be
inducing stressed conditions in the immune system similar to those observed during severe malaria and that parasite may
be displaying similar adaptive mechanisms. This study was carried out in collaboration with Prof. Jackson and Dr. Chua
(University of Melbourne).

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Figure 15
Analysis of the parasite transcriptome upon emerging from the liver shows the downregulation of 90 gene andupregulation of 2 genes. GO term analysis of downregulated genes highlighted terms associated with activationof the host immune system, consistent with the downregulation in the expression of several surface antigens.
Various transcription factors and metabolic processes were also inhibited.

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● Research achievements (FY 2014-2019)
1. International collaborative papers

Featured in journals: #210

(peer reviewed)
2. Other publications

Featured in journals: #100

3. Books published#5

4. Oral presentations

Keynote speeches/ invited lectures: #76
Other presentations: #18

5. Patent applications

Patent applications: #32 ( #12 in Japan,#20 overseas)

Patent registrations (of the above number): #26
6. Awards received#7

7. External grants#3

8. Gifts#4

9. Science outreach activities#31

10. Training#2

11. Collaboration with institutions#31

1. International collaborative papers (peer reviewed)
1.1

International collaborative papers co-authored with overseas affiliated universities：#75
i)Papers where "GI-CoRE" is stated as an affiliated institutionii) Papers which mention "Hokkaido University" in the acknowledgements
1)

Klopper M, Heupink TH, Hill-Cawthorne G, Streicher EM, Dippenaar A, de Vos M, Abdallah AM, Limberis J,
Merker M, Burns S, Niemann S, Dheda K, Posey J, Pain A, Warren RM: "A landscape of genomic alterations at theroot of a near-untreatable tuberculosis epidemic", BMC Med.,18(1):24(2020) i)

2)

Li P, Gandhi D, Mutas M, Ran YF, Carr M, Rampini S, Hall W, Lee GU: "Direct identification of the herpes
simplex virus UL27 gene through single particle manipulation and optical detection using a micromagnetic array",Nanoscale, (2020) i) ii)

3)

Ouchi Y, Mukai T, Koide K, Yamaguchi T, Park JH, Kim H, Yokoyama K, Tamaru A, Gordon SV, Nakajima C,
Suzuki Y: "WQ-3810: a new fluoroquinolone with a high potential against fluoroquinolone-resistant Mycobacterium
tuberculosis", Tuberculosis, 120(101891):101891(2020) i)

4)

Alasiri A, Abboud Guerr J, Hall WW, Sheehy N: "Novel Interactions between the Human T-Cell Leukemia Virus
Type 1 Antisense Protein HBZ and the SWI/SNF Chromatin Remodeling Family: Implications for Viral Life
Cycle", J Virol, 93(16) (2019) i)

5)Martini F, Arone C, Hasset A, Hall WW, Sheehy N: "The ESCRT-0 Protein HRS Interacts with the Human T Cell
Leukemia Virus Type 2 Antisense Protein APH-2 and Suppresses Viral Replication", J Virol, 94(1) (2019) i)

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6)

Anindita PD, Sasaki M, Gonzalez G, Phongphaew W, Carr M, Hang'ombe BM, Mweene AS, Ito K, Orba Y, Sawa
H: "Discovery and genetic characterization of diverse smacoviruses in Zambian non-human primates", Sci Rep,9(1):5045(2019). i)

7)

Auladell M, Jia X, Hensen L, Chua B, Fox A, Nguyen THO, Doherty PC, Kedzierska K: "Recalling the Future:
Immunological Memory Toward Unpredictable Influenza Viruses", Front Immunol, 10:1400 (2019). i)

8)Carr M, Gonzalez G, Martinelli A, Wastika CE, Ito K, Orba Y, Sasaki M, Hall WW, Sawa H: "Upregulated
expression of the antioxidant sestrin 2 identified by transcriptomic analysis of Japanese encephalitis virus-infected
SH-SY5Y neuroblastoma cells", Virus Genes, (2019) i) ii)

9)

Gonzalez G, Bair CR, Lamson DM, Watanabe H, Panto L, Carr MJ, Kajon AE: "Genomic characterization ofhuman adenovirus type 4 strains isolated worldwide since 1953 identifies two separable phylogroups evolving atdifferent rates from their most recent common ancestor", Virology, 538:11-23(2019) i)

10) Gonzalez G, Carr MJ, Kobayashi M, Hanaoka N, Fujimoto T: "Enterovirus-Associated Hand-Foot and Mouth
Disease and Neurological Complications in Japan and the Rest of the World", Int J Mol Sci, 20(20) (2019).i)11) Hala S, Antony CP, Alshehri M, Althaqafi AO, Alsaedi A, Mufti A, Kaaki M, Alhaj-Hussein BT, Zowawi HM, AlAmri A, Pain A: "First report of Klebsiella quasipneumoniae harboring bla KPC-2 in Saudi Arabia", Antimicrob
Resist Infect Cont, 8(203):019-0653(2019). i)
12) Hayashida K, Orba Y, Sequeira PC, Sugimoto C, Hall WW, Eshita Y, Suzuki Y, Runtuwene L, Brasil P, Calvet G,
Rodrigues CDS, Santos CCD, Mares-Guia MAM, Yamagishi J, Filippis AMB, Sawa H: "Field diagnosis andgenotyping of chikungunya virus using a dried reverse transcription loop-mediated isothermal amplification(LAMP) assay and MinION sequencing", PLoS Negl Trop Dis, 13(6):e0007480(2019) i)
13) Liu S, Liu X, Li J, Zhou H, Carr MJ, Zhang Z, Shi W: "Long noncoding RNAs: Novel regulators of virus-hostinteractions", Rev Med Virol, 29(4): e2046(2019) i)
14) Liu X, Zhang X, Li J, Zhou H, Carr MJ, Xing W, Zhang Z, Shi W: "Effects of Acetylshikonin on the Infection and
Replication of Coxsackievirus A16 in Vitro and in Vivo", J Nat Prod, 82(5):1089-1097(2019) i)
15) Marks ND, Winter AD, Gu HY, Maitland K, Gillan V, Ambroz M, Martinelli A, Laing R, MacLellan R, Towne J,
Roberts B, Hanks E, Devaney E, Britton C: "Profiling microRNAs through development of the parasitic nematode
Haemonchus identifies nematode-specific miRNAs that suppress larval development", Sci Rep, 9(1):01954154(2019). i)16) Mendis C, Thevanesam V, Kumara A, Wickramasinghe S, Madagedara D, Gamage C, Gordon SV, Suzuki Y,
Ratnatunga C, Nakajima C: "Insight into genetic diversity of Mycobacterium tuberculosis in Kandy, Sri Lanka
reveals predominance of the Euro-American lineage", Int J Infect Dis,87:84-91 (2019) i) ii)
17) Sanaki T, Wakabayashi M, Yoshioka T, Yoshida R, Shishido T, Hall WW, Sawa H, Sato A: "Inhibition of dengue
virus infection by 1-stearoyl-2-arachidonoyl-phosphatidylinositol in vitro", Faseb J, 33(12):13866-13881(2019) i)
ii)
18) Sekiya T, Mifsud EJ, Ohno M, Nomura N, Sasada M, Fujikura D, Daito T, Shingai M, Ohara Y, Nishimura T, Endo
M, Mitsumata R, Ikeda T, Hatanaka H, Kitayama H, Motokawa K, Sobue T, Suzuki S, Itoh Y, Brown LE,
Ogasawara K, Kino Y, Kida H: "Inactivated whole virus particle vaccine with potent immunogenicity and limited
IL-6 induction is ideal for influenza", Vaccine, 37(15):2158-2166(2019) i)ii)

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19) Takahashi K, Gonzalez G, Kobayashi M, Hanaoka N, Carr MJ, Konagaya M, Nojiri N, Ogi M, Fujimoto T:"Pediatric Infections by Human mastadenovirus C Types 2, 89, and a Recombinant Type Detected in Japan between
2011 and 2018", Viruses, 11(12) (2019). i) ii)
20) Tanikawa S, Tanino M, Wang L, Ishikawa M, Miyazaki M, Tsuda M, Orba Y, Sawa H, Matoba K, Nakamura N,
Nagashima K, Hall WW, Tanaka S: "Autopsy findings in the early stage of amyotrophic lateral sclerosis with"dropped head" syndrome", Neuropathology, 39(5):374-377 (2019) i)
21) Thapa J, Maharjan B, Malla M, Fukushima Y, Poudel A, Pandey BD, Hyashida K, Gordon SV, Nakajima C, Suzuki
Y: "Direct detection of Mycobacterium tuberculosis in clinical samples by a dry methyl green loop-mediatedisothermal amplification (LAMP) method", Tuberculosis, 117:1-6 (2019) i) ii)
22) Wang M, Li J, Yao MX, Zhang YW, Hu T, Carr MJ, Duchene S, Zhang XC, Zhang ZJ, Zhou H, Tong YG, Ding SJ,Wang XJ, Shi WF: "Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in
Shandong, China", Front Microbiol, 10:1001(2019) i)
23) Wastika CE, Sasaki M, Yoshii K, Anindita PD, Hang'ombe BM, Mweene AS, Kobayashi S, Kariwa H, Carr MJ,
Hall WW, Eshita Y, Orba Y, Sawa H: "Serological evidence of Zika virus infection in non-human primates inZambia", Arch Virol, 164(8):2165-2170(2019) i)
24) Zeeshan M, Shilliday F, Liu T, Abel S, Mourier T, Ferguson DJP, Rea E, Stanway RR, Roques M, Williams D,
Daniel E, Brady D, Roberts AJ, Holder AA, Pain A, Le Roch KG, Moores CA, Tewari R: "Plasmodium kinesin-8X
associates with mitotic spindles and is essential for oocyst development during parasite proliferation andtransmission", PLoS Pathog, 15(10)(2019). i)25) Zhang Z, Zhang X, Carr MJ, Zhou H, Li J, Liu S, Liu T, Xing W, Shi W: "A neonatal murine model ofcoxsackievirus A4 infection for evaluation of vaccines and antiviral drugs", Emerg Microbes Infect, 8(1):14451455(2019). i)
26) Latre De Late P, Haidar M, Ansari H, Tajeri S, Szarka E, Alexa A, Woods K, Remenyi A, Pain A, Langsley G:"Theileria highjacks JNK2 into a complex with the macroschizont GPI (GlycosylPhosphatidylInositol)-anchoredsurface protein p104", Cell Microbiol, 21(3):e12973(2019) i)
27) Doyle SR, Illingworth CJR, Laing R, Bartley DJ, Redman E, Martinelli A, Holroyd N, Morrison AA, Rezansoff A,
Tracey A, Devaney E, Berriman M, Sargison N, Cotton JA, Gilleard JS: “Population genomic and evolutionarymodelling analyses reveal a single major QTL for ivermectin drug resistance in the pathogenic nematode,
Haemonchus contortus”, BMC Genomics, 20(1):218 (2019) i)
28) Gaithuma AK, Yamagishi J, Martinelli A, Hayashida K, Kawai N, Marsela M, Sugimoto C: “A single test approach
for accurate and sensitive detection and taxonomic characterization of Trypanosomes by comprehensive analysis ofinternal transcribed spacer 1 amplicons”, PLoS Negl Trop Dis, 13(2): e0006842 (2019) i)
29) Hu T, Li J, Carr MJ, Duchêne S, Shi W: “The Asian Lineage of Zika Virus: Transmission and Evolution in Asia andthe Americas”, Virol Sin, 34(1), 1-8 (2019) i)
30) San LL, Aye KS, Oo NAT, Shwe MM, Fukushima Y, Gordon SV, Suzuki Y, Nakajima C: “Insight into
multidrug-resistant Beijing genotype Mycobacterium tuberculosis isolates in Myanmar”, Int J Infect Dis,
76:109-119 (2018) i) ii)

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31) Ishida Y, Tsuda M, Sawamura Y, Fujii K, Murai H, Horiuchi N, Orba Y, Sawa H, Hall WW, Nagashima K, Tanaka S:“Integrated diagnosis" of pilocytic astrocytoma: Molecular diagnostic procedure for an unusual case”, Pathol Int,
68(12):694-699 (2018) i) ii)
32) Zhang Z, Dong Z, Wang Q, Carr MJ, Li J, Liu T, Li D, Shi W: “Characterization of an inactivated whole-virus
bivalent vaccine that induces balanced protective immunity against coxsackievirus A6 and A10 in mice”, Vaccine,
36(46):7095-7104(2018) i)
33) Maharjan B, Nakajima C, Isoda N, Thapa J, Poudel A, Shah Y, Yamaguchi T, Shrestha B, Hoffmann H, Avsar K,
Shrestha A, Gordon SV, Suzuki Y: “Genetic diversity and distribution dynamics of multidrug-resistant
Mycobacterium tuberculosis isolates in Nepal”, Sci Rep, 8(1):16634 (2018) i) ii)
34) Ernest M, Hunja C, Arakura Y, Haraga Y, Abkallo HM, Zeng W, Jackson DC, Chua B, Culleton R: “The Toll-Like
Receptor 2 agonist PEG-Pam 2 Cys as an immunochemoprophylactic and immunochemotherapeutic against the liver
and transmission stages of malaria parasites”, Int J Parasitol Drugs Drug Resist, 8(3):451-458(2018)i)
35) Wang M, Ren Q, Zhang Z, Zhang L, Carr MJ, Li J, Zhou H, Shi W: “Rapid detection of hand, foot and mouthdisease enterovirus genotypes by multiplex PCR”, J Virol Methods, 258:7-12 (2018) i)
36) Fujiki J, Nobori H, Sato A, Sasaki M, Carr M, Hall WW, Orba Y, Sawa H: “Single amino acid mutation in dengue
virus NS4B protein has opposing effects on viral proliferation in mammalian and mosquito cells”, Jpn J Infect Dis,
71(6):448-454 (2018) i)
37) Sasaki M, Kajihara M, Changula K, Mori-Kajihara A, Ogawa H, Hang’ombe, BM, Mweene AS, Simuunza M,
Yoshida R, Carr M, Orba Y, Takada A, Sawa H: “ Identification of group A rotaviruses from Zambian fruit batsprovides evidence for long-distance transmission events in Africa”, Infect Genet Evol, 63:104-109 (2018) i)
38) Nobori H, Toba S, Yoshida R, Hall WW, Orba Y, Sawa H, Sato A: “Identification of Compound-B, a novel antidengue virus agent targeting the non-structural protein 4A”, Antiviral Res, 155:60-66 (2018) i)
39) Schuelein R, Spencer H, Dagley LF, Li PF, Luo L, Stow JL, Abraham G, Naderer T, Gomez-Valero L, Buchrieser C,
Sugimoto C, Yamagishi J, Webb AI, Pasricha S, Hartland EL: “Targeting of RNA Polymerase II by a nuclear

Legionella pneumophila Dot/Icm effector SnpL”, Cell Microbiol, 20(9):e12852 (2018) i) ii)
40) Orba Y, Hang'ombe BM, Mweene AS, Wada Y, Anindita PD, Phongphaew W, Qiu Y, Kajihara M, Mori-Kajihara A,
Eto Y, Sasaki M, Hall WW, Eshita Y, Sawa H: “First isolation of West Nile virus in Zambia from mosquitoes”,
Transbound Emerg Dis, 65(4):933-938 (2018) i)
41) Torii S, Orba Y, Hang'ombe BM, Mweene AS, Wada Y, Anindita PD, Phongphaew W, Qiu Y, Kajihara M, MoriKajihara A, Eto Y, Harima H, Sasaki M, Carr M, Hall WW, Eshita Y, Abe T, Sawa H: “Discovery of Mwinilungaalphavirus: a novel alphavirus in Culex mosquitoes in Zambia”, Virus Res, 250:31-36 (2018) i)
42) Sasaki M, Anindita PD, Ito N, Sugiyama M, Carr M, Fukuhara H, Ose T, Maenaka K, Takada A, Hall WW, Orba Y,
Sawa H: “Role of Heparan sulfate proteoglycans serve as an attachment factor for rabies virus entry and infection”,
J Infect Dis, 217(11):1740-1749 (2018) i)
43) Tawe L, Motshoge T, Ramatlho P, Mutukwa N, Muthoga CW, Dongho GBD, Martinelli A, Peloewetse E, Russo G,
Quaye IK, Paganotti GM: “Human cytochrome P450 2B6 genetic variability in Botswana: a case of haplotype
diversity and convergent phenotypes”, Sci Rep, 8(1):4912 (2018) i)

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44) Narulla MS, Alasiri A, Charmier L, Noonan S, Conroy D, Hall WW, Sheehy N: “Erratum for Narulla et al., "Positive
and Negative Regulation of Type I Interferons by the Human T Cell Leukemia Virus Antisense Protein HBZ”, J
Virol, 92(2). pii: e01865-17 (2018) i)
45) Chua BY, Sekiya T, Jackson DC: “Opinion: Making Inactivated and Subunit-Based Vaccines Work”, Viral
Immunol, 31(2):150-158 (2018) i)
46) Dong ZP, Wang Q, Zhang ZJ, Carr MJ, Li D, Shi WF: “Murine model of acute myocarditis and cerebral corticalneuron edema induced by coxsackievirus B4”, Zool Res, 39(1):52-57 (2018) i)
47) Sasaki M, Anindita PD, Phongphaew W, Carr M, Kobayashi S, Orba Y, Sawa H: “Development of a rapid andquantitative method for the analysis of viral entry and release using a NanoLuc luciferase complementation assay”,
Virus Res, 243, 69-74 (2018) i)
48) Nguyen LT, Van Nguyen D, Carr MJ, Hall WW, Nguyen LA: “Association of interferon lambda polymorphisms
with elevated baseline viral loads in chronic hepatitis C virus genotype 6 infection”, Arch Virol, 163(1), 115-124(2018) i)49) Haidar M, Rchiad Z, Ansari HR, Ben-Rached F, Tajeri S, Latre De Late P, Langsley G, Pain A: “miR-126-5p bydirect targeting of JNK-interacting protein-2 (JIP-2) plays a key role in Theileria-infected macrophage virulence”,
PLoS Pathog. 23;14(3), e1006942 (2018) i)
50) Coll F, Phelan J, Hill-Cawthorne GA, Nair MB, Mallard K, Ali S, Abdallah AM, Alghamdi S, Alsomali M, Ahmed
AO, Portelli S, Oppong Y, Alves A, Bessa TB, Campino S, Caws M, Chatterjee A, Crampin AC, Dheda K, Furnham
N, Glynn JR, Grandjean L, Minh Ha D, Hasan R, Hasan Z, Hibberd ML, Joloba M, Jones-López EC, Matsumoto T,
Miranda A, Moore DJ, Mocillo N, Panaiotov S, Parkhill J, Penha C, Perdigão J, Portugal I, Rchiad Z, Robledo J,
Sheen P, Shesha NT, Sirgel FA, Sola C, Oliveira Sousa E, Streicher EM, Helden PV, Viveiros M, Warren RM,
McNerney R, Pain A, Clark TG: “Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium
tuberculosis” Nat Genet., 50(2), 307-316 (2018) i)
51) Martinelli A, Culleton R: “Non-human Primate Malaria Parasites: out of the forest and into the laboratory”,
Parasitology, 41-54. (2017) i)
52) Sekiya T, Yamagishi J, Gray JHV, Whitney PG, Martinelli A, Zeng W, Wong CY, Sugimoto C, Jackson DC, Chua
BY : “PEGylation of a TLR2-agonist-based vaccine delivery system improves antigen trafficking and the magnitudeof ensuing antibody and CD8 + T cell responses”, Biomaterials, 137, 61-72 (2017) i) ii)
53) Wijayadikusumah AR, Sullivan LC, Jackson DC, Chua BY : “Structure-function relationships of protein-lipopeptide
complexes and influence on immunogenicity”, Amino Acids, 49(10), 1691-1704 (2017) i)
54) Wada Y, Orba Y, Sasaki M, Kobayashi S, Carr MJ, Nobori H, Sato A, Hall WW, Sawa H: “Discovery of a novel
antiviral agent targeting the nonstructural protein 4 (nsP4) of chikungunya virus”, Virology, 505, 102-112(2017) i)
55) Carr M, Gonzalez G, Sasaki M, Dool SE, Ito K, Ishii A, Hang'ombe BM, Mweene AS, Teeling EC, Hall WW, Orba
Y, Sawa H: “Identification of the same polyomavirus species in different African horseshoe bat species is indicativeof short-range host-switching events”, J Gen Virol, 98(11), 2771-2785 (2017) i)
56) Carr M, Gonzalez G, Sasaki M, Ito K, Ishii A, Hang'ombe BM, Mweene AS, Orba Y, Sawa H : “Discovery ofAfrican bat polyomaviruses and infrequent recombination in the large T antigen in the Polyomaviridae”, J Gen
Virol, 98(4), 726-738 (2017) i)

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57) Zhang Z, Dong Z, Wei Q, Carr MJ, Li J, Ding S, Tong Y, Li D, Shi W: “A Neonatal Murine Model of Coxsackievirus
A6 Infection for Evaluation of Antiviral and Vaccine Efficacy”, J Virol, 91(9) (2017) i)
58) Zhang Z, Dong Z, Li J, Carr MJ, Zhuang D, Wang J, Zhang Y, Ding S, Tong Y, Li D, Shi W: “Protective efficacy offormaldehyde-inactivated whole-virus vaccine and antivirals in a murine model of coxsackievirus A10 infection”, J
Virol, 91 (13) (2017) i)
59) Wang J, Hu T, Sun D, Ding S, Carr MJ, Xing W, Li S, Wang X, Shi W: “Epidemiological Characteristics of Hand,
Foot, and Mouth Disease in Shandong, China, 2009-2016”, Sci Rep, 7(1), 8900 (2017) i)
60) Abkallo HM, Martinelli A, Inoue M, Ramaprasad A, Xangsayarath P, Gitaka J, Tang J, Yahata K, Zoungrana A,
Mitaka H, Acharjee A, Datta PP, Hunt P, Carter R, Kaneko O, Mustonen V, Illingworth CJR, Pain A, Culleton R :“Rapid identification of genes controlling virulence and immunity in malaria parasites”, PLoS Pathog, 13(7),e1006447 (2017) i)
61) Abd El Ghany M, Alsomali M, Almasri M, Padron Regalado E, Naeem R, Tukestani A, Asiri A, Hill-Cawthorne
GA, Pain A, Memish ZA: “Enteric Infections Circulating during Hajj Seasons, 2011-2013”, Emerg Infect Dis, 23(10)(2017) i)
62) Jackson DC, Zeng W, Wong CY, Mifsud EJ, Williamson NA, Ang CS, Vingrys AJ, Downie LE: “Tear InterferonGamma as a Biomarker for Evaporative Dry Eye Disease”, Invest Ophthalmol Visual Sci,57(11):4824-4830 (2016)i)63) Lv Q, Zhang H, Tian L, Zhang R, Zhang Z, Li J, Tong Y, Fan H, Carr MJ, Shi W: “Novel sub-lineages, recombinants
and reassortants of severe fever with thrombocytopenia syndrome virus”, Ticks Tick Borne Dis, 8(3), 385-390 (2017)i)64) Carr M, Kawaguchi A, Sasaki M, Gonzalez G, Ito K, Thomas Y, Hang’ombe BM, Mweene AS, Zhao G, Wang D,
Orba Y, Ishii A, Sawa H : “Isolation of a simian immunodeficiency virus from a malbrouck (Chlorocebus
cynosuros)”, Arch Virol, 162(2), 543-548 (2017) i)
65) Phongphaew W, Kobayashi S, Sasaki M, Carr M, Hall WW, Orba Y, Sawa H: “Valosin-containing protein(VCP/p97) plays a role in the replication of West Nile virus”, Virus Res, 228, 114-123(2017) i)
66) Anindita PD, Sasaki M, Nobori H, Sato A, Carr M, Ito N, Sugiyama M, Orba Y, Sawa H: “Generation of recombinantrabies viruses encoding NanoLuc luciferase for antiviral activity assays.”, Virus Res, 215,121-8(2016) i)
67) Shi W, Zhang Z, Ling C, Carr MJ, Tong Y, Gao GF: “ Increasing genetic diversity of Zika virus in the Latin American
outbreak”, Emerg Microbes Infect, 5, e68 (2016) i）
68) Ansar HR, Templeton TJ, Subudhi AK, Ramaprasad A, Tang J Lu F, Naeem R, Hashish Y, Oguikee MC, Benaventef
ED, Clark TG, Sutherland CJ, Bardwell JW, Culleton R, Cao J, Pain A: “Genome-scale comparison of expanded genefamilies in Plasmodium ovale wallikeri and Plasmodium ovale curtisi with Plasmodium malariae and with other
Plasmodium species.” Int. J. of Parasitology, doi:10.1016 /j.ijpara (2016) i）
69) Rao PN, Santos JM, Pain A, Templeton TJ, Mair GR: “Translational repression of the cpw-wpc gene family in themalaria parasite Plasmodium.” Parasitol Int,14;65(5 Pt A):463-471 (2016) i）
70) Moon RW, Sharaf H, Hastings CH, Ho YS, Nair MB, Rchiad Z, Knuepfer E, Ramaprasad A, Mohring F, Amir A,
Yusuf NA, Hall J, Almond N, Lau YL, Pain A, Blackman MJ, Holder AA: “ Normocyte-binding protein required forhuman erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi.”, Proc Natl Acad Sci U S A,
113(26):7231-6 (2016) i）

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71) Chua BY, Wong CY, Mifsud EJ, Edenborough KM, Sekiya T, Tan AC, Mercuri F, Rockman S, Chen W, Turner SJ,
Doherty PC, Kelso A, Brown LE, Jackson DC: “Inactivated influenza vaccine that provides rapid, innate-immunesystem-mediated protection and subsequent long-term adaptive immunity”, MBio,6(6). Pii,e01024-15 (2015) i）
72) Gornik SG, Febrimarsa, Cassin AM, MacRae JI, Ramaprasad A, Rchiad Z, McConville MJ, Bacic A, McFadden
GI, Pain A, Waller RF : “Endosymbiosis undone by stepwise elimination of the plastid in a parasitic dinoflagellate”,
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73) Assefa S, Lim C, Preston MD, Duffy CW, Nair MB, Adroub SA, Kadir KA, Goldberg JM, Neafsey DE, Divis P,
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Pain A: “Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly
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1.2

International collaborative papers：#135
i) Papers where "GI-CoRE" is stated as an affiliated institutionii) Papers which mention "Hokkaido University" in the acknowledgements

1) Solo ES, Nakajima C, Kaile T, Bwalya P, Mbulo G, Fukushima Y, Chila S, Kapata N, Shah Y, Suzuki Y: “Mutationsof rpoB, katG and inhA genes in multidrug-resistant Mycobacterium tuberculosis isolates from Zambia”, J Glob
Antimicrob Resist. 2020 Mar 10. pii: S2213-7165(20)30055-2. doi: 10.1016/j.jgar.2020.02.026. [Epub ahead of print](2020) i) ii)
2) Tetsuo M, Matsuno K, Tamura T, Fukuhara T, Kim T, Okamatsu M, Tautz N, Matsuura Y, Sakoda Y: "Developmentof a High-Throughput Serum Neutralization Test Using Recombinant Pestiviruses Possessing a Small Reporter Tag",
Pathogens, 9(3) (2020) i)
3) Phetsuksiri B, Rudeeaneksin J, Srisungngam S, Bunchoo S, Klayut W, Nakajima C, Hamada S, Suzuki Y:"Comparison of Loop-Mediated Isothermal Amplification, Microscopy, Culture, and PCR for Diagnosis of
Pulmonary Tuberculosis", Jpn Infect Dis. doi: 10.7883/yoken.JJID.2019.335. [Epub ahead of print] (2020) i) ii)
4) Harima H, Kajihara M, Simulundu E, Bwalya E, Qiu Y, Isono M, Okuya K, Gonzalez G, Yamagishi J, Hang'ombe
BM, Sawa H, Mweene AS, Takada A: "Genetic and Biological Diversity of Porcine Sapeloviruses Prevailing in
Zambia", Viruses, 12(2) (2020) i)
5) Kikutani Y, Okamatsu M, Nishihara S, Takase-Yoden S, Hiono T, de Vries RP, McBride R, Matsuno K, Kida H,
Sakoda Y: "E190V substitution of H6 hemagglutinin is one of key factors for binding to sulfated sialylated glycan
receptor and infection to chickens", Microbiol Immunol, (2020) i)

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6) Twabela AT, Okamatsu M, Tshilenge GM, Mpiana S, Masumu J, Nguyen LT, Matsuno K, Monne I, Zecchin B,
Sakoda Y: "Molecular, antigenic, and pathogenic characterization of H5N8 highly pathogenic avian influenza viruses
isolated in the Democratic Republic of Congo in 2017", Arch Virol, 165(1):87-96(2020). i)7) Itakura Y, Matsuno K, Ito A, Gerber M, Liniger M, Fujimoto Y, Tamura T, Kameyama KI, Okamatsu M, Ruggli N,
Kida H, Sakoda Y: "A cloned classical swine fever virus derived from the vaccine strain GPE(-) causes cytopathic
effect in CPK-NS cells via type-I interferon-dependent necroptosis", Virus Res, 276(197809):9(2020). i) ii)
8) Takadate Y, Kondoh T, Igarashi M, Maruyama J, Manzoor R, Ogawa H, Kajihara M, Furuyama W, Sato M,
Miyamoto H, Yoshida R, Hill TE, Freiberg AN, Feldmann H, Marzi A, Takada A: "Niemann-Pick C1 Heterogeneityof Bat Cells Controls Filovirus Tropism", Cell Rep, 30(2):308-319(2020). i)
9) Kajihara M, Hang'ombe BM, Changula K, Harima H, Isono M, Okuya K, Yoshida R, Mori-Kajihara A, Eto Y,
Orba Y, Ogawa H, Qiu Y, Sawa H, Simulundu E, Mwizabi D, Munyeme M, Squarre D, Mukonka V, Mweene A,
Takada A: “Marburgvirus in Egyptian Fruit Bats”, Zambia, Emerg Infect Dis, 25(8), 1577-1580 (2019)10) Temuujin U, Tserendorj A, Fujiki J, Sakoda Y, Tseren-Ochir EO, Okamatsu M, Matsuno K, Sharav T, Horiuchi M,
Umemura T, Chultemdorj T: “The first isolation and identification of canine parvovirus (CPV) type 2c variants during
2016-2018 genetic surveillance of dogs in Mongolia”, Infect Genet Evol, 73: 269-275 (2019)11) Abudurexiti A, Adkins S, Alioto D, Alkhovsky SV, Avsic-Zupanc T, Ballinger MJ, Bente DA, Beer M, Bergeron E,
Blair CD, Briese T, Buchmeier MJ, Burt FJ, Calisher CH, Chang C, Charrel RN, Choi IR, Clegg JCS, de la Torre JC,
de Lamballerie X, Deng F, Di Serio F, Digiaro M, Drebot MA, Duan X, Ebihara H, Elbeaino T, Ergunay K, Fulhorst
CF, Garrison AR, Gao GF, Gonzalez JJ, Groschup MH, Gunther S, Haenni AL, Hall RA, Hepojoki J, Hewson R, Hu
Z, Hughes HR, Jonson MG, Junglen S, Klempa B, Klingstrom J, Kou C, Laenen L, Lambert AJ, Langevin SA, Liu
D, Lukashevich IS, Luo T, Lu C, Maes P, de Souza WM, Marklewitz M, Martelli GP, Matsuno K, Mielke-Ehret N,
Minutolo M, Mirazimi A, Moming A, Muhlbach HP, Naidu R, Navarro B, Nunes MRT, Palacios G, Papa A,
Pauvolid-Correa A, Paweska JT, Qiao J, Radoshitzky SR, Resende RO, Romanowski V, Sall AA, Salvato MS,
Sasaya T, Shen S, Shi X, Shirako Y, Simmonds P, Sironi M, Song JW, Spengler JR, Stenglein MD, Su Z, Sun S,
Tang S, Turina M, Wang B, Wang C, Wang H, Wang J, Wei T, Whitfield AE, Zerbini FM, Zhang J, Zhang L, Zhang
Y, Zhang YZ, Zhou X, Zhu L, Kuhn JH: "Taxonomy of the order Bunyavirales: update 2019", Arch Virol,
164(7):1949-1965(2019) i)
12) Hajake T, Matsuno K, D MK, Oda H, Kobayashi M, Miyata N, Shinji M, Kogure A, Kasajima N, Okamatsu M,
Sakoda Y, Kato H, Fujita T: "Broad and systemic immune-modulating capacity of plant-derived dsRNA", Int
Immunol, 31(12):811-821 (2019) i)
13) Halawi AD, Saasa N, Pongombo BL, Kajihara M, Chambaro HM, Hity M, Sawa H, Takada A, Mweene AS, Nsembo
LL, Simulundu E: "Seroprevalence of Rift Valley fever in cattle of smallholder farmers in Kwilu Province in the
Democratic Republic of Congo", Trop Anim Health Prod, 51(8):2619-2627 (2019) i)
14) Harima H, Sasaki M, Kajihara M, Mori-Kajihara A, Hang'ombe BM, Changula K, Orba Y, Ogawa H, Simuunza M,
Yoshida R, Mweene A, Takada A, Sawa H: "Detection of novel orthoreovirus genomes in shrew (Crocidura hirta)
and fruit bat (Rousettus aegyptiacus)", J Vet Med Sci, 20(10):19-0424(2019). i)
15) Ito S, Jurado C, Bosch J, Ito M, Sanchez-Vizcaino JM, Isoda N, Sakoda AY: "Role of Wild Boar in the Spread ofClassical Swine Fever in Japan", Pathogens, 8(4) (2019). i)

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16) Ito S, Jurado C, Sanchez-Vizcaino JM, Isoda N: "Quantitative risk assessment of African swine fever virus
introduction to Japan via pork products brought in air passengers’luggage", Transbound Emerg Dis,
6(10):13414(2019). i) ii)
17) Kim H, Fukutomi Y, Nakajima C, Kim YU, Mori S, Shibayama K, Nakata N, Suzuki Y: "DNA gyrase could be a
crucial regulatory factor for growth and survival of Mycobacterium leprae", Sci Rep, 9(1):10815(2019) i) ii)
18) Koide K, Kongsoi S, Nakajima C, Suzuki Y: "WQ-3810 exerts high inhibitory effect on quinolone-resistant DNA
gyrase of Salmonella Typhimurium", Biosci Biotechnol Biochem:83(12):2249-2256 (2019) i)
19) Le KT, Okamatsu M, Nguyen LT, Matsuno K, Chu DH, Tien TN, Le TT, Kida H, Sakoda Y: "Genetic and antigenic
characterization of the first H7N7 low pathogenic avian influenza viruses isolated in Vietnam", Infect Genet Evol,
78(104117):104117(2019). i) ii)
20) Makiala S, Mukadi D, De Weggheleire A, Muramatsu S, Kato D, Inano K, Gondaira F, Kajihara M, Yoshida R,
Changula K, Mweene A, Mbala-Kingebeni P, Muyembe-Tamfum JJ, Masumu J, Ahuka S, Takada A: "Clinical
Evaluation of QuickNavi(TM)-Ebola in the 2018 Outbreak of Ebola Virus Disease in the Democratic Republic of theCongo", Viruses, 11(7)(2019). i)21) Moonga LC, Hayashida K, Nakao R, Lisulo M, Kaneko C, Nakamura I, Eshita Y, Mweene AS, Namangala B,
Sugimoto C, Yamagishi J: "Molecular detection of Rickettsia felis in dogs, rodents and cat fleas in Zambia", Parasit
Vectors, 12(1):168(2019) i) ii)
22) Muleya W, Chambaro HM, Sasaki M, Gwenhure LF, Mwenechanya R, Kajihara M, Saasa N, Mupila Z, MoriKajihara A, Qiu Y, Kangwa E, Mweene A, Namangala B, Takada A, Sawa H: "Genetic diversity of rabies virus indifferent host species and geographic regions of Zambia and Zimbabwe", Virus Genes,55(5):713-719 (2019) i) ii)
23) Nakagawa S, Inoue S, Kryukov K, Yamagishi J, Ohno A, Hayashida K, Nakazwe R, Kalumbi M, Mwenya D, Asami
N, Sugimoto C, Mutengo MM, Imanishi T: "Rapid sequencing-based diagnosis of infectious bacterial species frommeningitis patients in Zambia", Clin Transl Immunology, 8(11) (2019). i) ii)
24) Nakamura Y, Yamagishi J, Hayashida K, Osada N, Chatanga E, Mweempwa C, Chilongo K, Chisi J, Musaya J,
Inoue N, Namangala B, Sugimoto C: "Genetic diversity and population structure of Glossina morsitans morsitans in
the active foci of human African trypanosomiasis in Zambia and Malawi", PLoS Negl Trop Dis,
13(7):e0007568(2019) i)
25) Nguyen LT, Firestone SM, Stevenson MA, Young ND, Sims LD, Chu DH, Nguyen TN, Van Nguyen L, Thanh Le T,
Van Nguyen H, Nguyen HN, Tien TN, Nguyen TD, Tran BN, Matsuno K, Okamatsu M, Kida H, Sakoda Y: "Asystematic study towards evolutionary and epidemiological dynamics of currently predominant H5 highly pathogenic
avian influenza viruses in Vietnam", Sci Rep, 9(1):019-42638(2019). i)
26) Nguyen LT, Stevenson MA, Firestone SM, Sims LD, Chu DH, Nguyen LV, Nguyen TN, Le KT, Isoda N, Matsuno
K, Okamatsu M, Kida H, Sakoda Y: "Spatiotemporal and risk analysis of H5 highly pathogenic avian influenza in
Vietnam, 2014-2017", Prev Vet Med, 22(104678):007(2019). i)27) Qiu Y, Kajihara M, Harima H, Hang'ombe BM, Nakao R, Hayashida K, Mori-Kajihara A, Changula K, Eto Y, Ndebe
J, Yoshida R, Takadate Y, Mwizabi D, Kawabata H, Simuunza M, Mweene A, Sawa H, Takada A, Sugimoto C:"Molecular characterization and phylogenetic analysis of Trypanosoma spp. detected from striped leaf-nosed bats
(Hipposideros vittatus) in Zambia", Int J Parasitol Parasites Wildl, 9:234-238(2019) i)

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28) Qiu Y, Nakao R, Hang'ombe BM, Sato K, Kajihara M, Kanchela S, Changula K, Eto Y, Ndebe J, Sasaki M, Thu MJ,
Takada A, Sawa H, Sugimoto C, Kawabata H: "Human Borreliosis Caused by a New World Relapsing Fever
Borrelia-like Organism in the Old World", Clin Infect Dis, 69(1):107-112(2019) i)
29) Shah Y, Poudel A, Maharjan B, Thapa J, Yamaguchi T, Diab HM, Pandey BD, Solo E, Isoda N, Suzuki Y, Nakajima
C: "Genetic diversity of Mycobacterium tuberculosis Central Asian Strain isolates from Nepal and comparison withneighboring countries", Trans R Soc Trop Med Hyg, 113(4):203-211(2019) i)
30) Thu MJ, Qiu Y, Kataoka-Nakamura C, Sugimoto C, Katakura K, Isoda N, Nakao R: "Isolation of Rickettsia,
Rickettsiella, and Spiroplasma from Questing Ticks in Japan Using Arthropod Cells", Vector Borne Zoonotic Dis,
19(7):474-485(2019) i)
31) Whelan MVX, Ardill L, Koide K, Nakajima C, Suzuki Y, Simpson JC, O'Croinin T: “Acquisition of fluoroquinolone
resistance leads to increased biofilm formation and pathogenicity in Campylobacter jejuni”, Sci Rep, 9(1):18216(2019). i)
32) Paudel S, Nakajima C, Mikota SK, Gairhe KP, Maharjan B, Subedi S, Poudel A, Sashika M, Shimozuru M, Suzuki Y,
Tsubota T: “Mixed Mycobacterium tuberculosis Lineage Infection in 2 Elephants, Nepal”, Emerg Infect Dis.
25(5):1031-1032 (2019) ii)
33) Usui M, Yokoo H, Tamura Y, Nakajima C, Suzuki Y, Ghigo JM, Beloin C: “Zinc Acetate Potentiates the Action of
Tosufloxacin against Escherichia coli Biofilm Persisters”, Antimicrob Agents Chemother, 63(6) (2019)34) Bazarragchaa E, Okamatsu M, Ulaankhuu A, Twabela AT, Matsuno K, Kida H, Sakoda Y: "Evaluation of a rapid
isothermal nucleic acid amplification kit, Alere i Influenza A&B, for the detection of avian influenza viruses", J
Virol Methods, 265:121-125(2019) i)
35) Koide K, Kongsoi S, Ouchi Y, Yamaguchi T, Nakajima C, Suzuki Y: "Antibacterial Activity of DC-159a Against
Salmonella Typhimurium", Microb Drug Resist, 25(1):14-22(2019) i) ii)
36) Qiu Y, Abe T, Nakao R, Satoh K, Sugimoto C: "Viral population analysis of the taiga tick, Ixodes persulcatus, byusing Batch Learning Self-Organizing Maps and BLAST search", J Vet Med Sci, 81(3):401-410(2019) i)
37) Torii S, Matsuno K, Qiu Y, Mori-Kajihara A, Kajihara M, Nakao R, Nao N, Okazaki K, Sashika M, Hiono T,
Okamatsu M, Sakoda Y, Ebihara H, Takada A, Sawa H: "Infection of newly identified phleboviruses in ticks andwild animals in Hokkaido, Japan indicating tick-borne life cycles", Ticks Tick Borne Dis, 10(2):328-335(2019) i) ii)
38) Phetsuksiri B, Rudeeaneksin J, Srisungngam S, Bunchoo S, Klayut W, Sangkitporn S, Nakajima C, Hamada S, Suzuki
Y: “Loop-mediated isothermal amplification for rapid identification of Mycobacterium tuberculosis in comparison withimmunochromatographic SD Bioline MPT64 Rapid® in a high burden setting” Jpn J Infect Dis. 25:72(2):112-114(2019) i)
39) Davaasuren B, Yamagishi J, Mizushima D, Narantsatsral S, Otgonsuren D, Myagmarsuren P, Battsetseg B, Battur B,
Inoue N, Suganuma K: “Draft Genome Sequence of Trypanosoma equiperdum Strain IVM-t1”, Microbiol Resour
Announc, 8(9) (2019) i)
40) Thu MJ, Qiu Y, Matsuno K, Kajihara M, Mori-Kajihara A, Omori R, Monma N, Chiba K, Seto J, Gokuden M, Andoh
M, Oosako H, Katakura K, Takada A, Sugimoto C, Isoda N, Nakao R: “Diversity of spotted fever group rickettsiae

and their association with host ticks in Japan”, Sci Rep, 9(1):1500 (2019) i)

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41) Sato M, Maruyama J, Kondoh T, Nao N, Miyamoto H, Takadate Y, Furuyama W, Kajihara M, Ogawa H, Manzoor R,
Yoshida R, Igarashi M, Takada A: “Generation of bat-derived influenza viruses and their reassortants” Sci Rep,9(1):1158 (2019) i)
42) HiSivakumar T, Tuvshintulga B, Zhyldyz A, Kothalawala H, Yapa PR, Kanagaratnam R, Vimalakumar SC, Abeysekera
TS, Weerasingha AS, Yamagishi J, Igarashi I, Silva SSP, Yokoyama N: “Genetic analysis of Babesia isolates from cattlewith clinical babesiosis in Sri Lanka”, J Clin Microbiol, 48(12):915-924 (2018) i)
43) Borthong J, Omori R, Sugimoto C, Suthienkul O, Nakao R, Ito K: “Comparison of Database Search Methods for the
Detection of Legionella pneumophila in Water Samples Using Metagenomic Analysis”, Front Microbiol, 9:1272(2018) i)
44) Thida Oo NA, San LL, Thapa J, Aye KS, Aung WW, Nakajima C, Suzuki Y: “Characterization of mutations conferring
streptomycin resistance to multidrug-resistant Mycobacterium tuberculosis isolates from Myanmar”, Tuberculosis,
111:8-13 (2018) i) ii)
45) Wang ZJ, Kikutani Y, Nguyen LT, Hiono T, Matsuno K, Okamatsu M, Krauss S, Webby R, Lee YJ, Kida H, Sakoda Y:“H13 influenza viruses in wild birds have undergone genetic and antigenic diversification in nature”, Virus Genes,
54(4):543-549 (2018) i) ii)
46) Imai K, Tarumoto N, Runtuwene LR, Sakai J, Hayashida K, Eshita Y, Maeda R, Tuda J, Ohno H, Murakami T, Maesaki
S, Suzuki Y, Yamagishi J, Maeda T: “An innovative diagnostic technology for the codon mutation C580Y in kelch13
of Plasmodium falciparum with MinION nanopore sequencer”, Malar J, 17(1), 217 (2018) i)
47) Runtuwene LR, Tuda JSB, Mongan AE, Makalowski W, Frith MC, Imwong M, Srisutham S, Nguyen Thi LA, Tuan
NN, Eshita Y, Maeda R, Yamagishi J, Suzuki Y: “Nanopore sequencing of drug-resistance-associated genes in malaria
parasites, Plasmodium falciparum.”, Sci Rep, 8(1), 8286 (2018) i)
48) Marzi A, Haddock E, Kajihara M, Feldmann H, Takada A: “Monoclonal Antibody Cocktail Protects Hamsters From
Lethal Marburg Virus Infection”, J Infect Dis, 218(suppl_5): S662-S665 (2018) i)
49) Changula K, Kajihara M, Mori-Kajihara A, Eto Y, Miyamoto H, Yoshida R, Shigeno A, Hang'ombe B, Qiu Y, Mwizabi
D, Squarre D, Ndebe J, Ogawa H, Harima H, Simulundu E, Moonga L, Kapila P, Furuyama W, Kondoh T, Sato M,
Takadate Y, Kaneko C, Nakao R, Mukonka V, Mweene A, Takada A: “Seroprevalence of Filovirus Infection of
Rousettus aegyptiacus Bats in Zambia”, J Infect Dis,218(suppl_5):S312-S317 (2018) i) ii)
50) Kondoh T, Letko M, Munster VJ, Manzoor R, Maruyama J, Furuyama W, Miyamoto H, Shigeno A, Fujikura D,
Takadate Y, Yoshida R, Igarashi M, Feldmann H, Marzi A, Takada A: “Single-Nucleotide Polymorphisms in Human
NPC1 Influence Filovirus Entry Into Cells”, J Infect Dis, 218(suppl_5):S397-S402 (2018) i) ii)
51) Matsuno K, Kajihara M, Nakao R, Nao N, Mori-Kajihara A, Muramatsu M, Qin Y, Torii S, Igarashi M, Kasajima N,
Mizume K, Yoshii K, Sawa H, Sugimoto C, Takada A, Ebihara H: “ The unique phylogenetic position of a novel tickborne phlebovirus ensures an ixodid origin of the genus Phlebovirus”, mSphere, 3(3). pii: e00239-18 (2018) i) ii)
52) Qiu Y, Kaneko C, Kajihara M, Ngonda S, Simulundu E, Muleya W, Thu MJ, Hang'ombe MB, Katakura K, Takada A,
Sawa H, Simuunza M, Nakao R: “Tick-borne haemoparasites and Anaplasmataceae in domestic dogs in Zambia”,
Ticks Tick Borne Dis, 9(4),988-995(2018) i)
53) Fujihira H, Usami K, Matsuno K, Takeuchi H, Denda-Nagai K, Furukawa J, Shinohara Y, Takada A, Kawaoka Y,
Irimura T: “A Critical Domain of Ebolavirus Envelope Glycoprotein Determines Glycoform and Infectivity”, Sci Rep
8, 5495(2018) i)

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54) Saasa N, Kajihara M, Dautu G, Mori-Kajihara A, Fukushi S, Sinkala Y, Morikawa S, Mweene A, Takada A, Yoshimatsu
K, Arikawa J: “Expression of a recombinant nucleocapsid protein of Rift Valley 1 fever virus in Vero cells as an
immunofluorescence antigen and its use for sero-surveillance in traditional cattle herds in Zambia”, Vector Borne
Zoonotic Dis, 18(5):273-277 (2018) i)
55) Donovan PD, Gonzalez G, Higgins DG, Butler G, Ito K: “Identification of fungi in shotgun metagenomics datasets”,
PLoS One, 13(2),e0192898 (2018) i)
56) Wada Y, Sasaki M, Setiyono A, Handharyani E, Rahmadani I, Taha S, Adiani S, Latief M, Kholilullah ZA, Subangkit
M, Kobayashi S, Nakamura I, Kimura T, Orba Y, Sawa H: “Detection of novel gammaherpesviruses from fruit bats inIndonesia”, J Med Microbiol, 67(3),415-422(2018) i)
57) Simulundu E, Chambaro HM, Sinkala Y, Kajihara M, Ogawa H, Mori A, Ndebe J, Dautu G, Mataa L, Lubaba CH,
Simuntala C, Fandamu P, Simuunza M, Pandey GS, Samui KL, Misinzo G, Takada A, Mweene AS, “Co-circulation ofmultiple genotypes of African swine fever viruses among domestic pigs in Zambia (2013-2015)”, Transbound Emerg
Dis, 65(1):114-122 (2018) i)
58) Vlahakis PA, Chitanga S, Simuunza MC, Simulundu E, Qiu Y, Changula K, Chambaro HM, Kajihara M, Nakao R,
Takada A, Mweene AS: “Molecular detection and characterization of zoonotic Anaplasma species in domestic dogs in
Lusaka, Zambia”, Ticks Tick Borne Dis, 9(1):39-43 (2018) i)
59) Liu M, Adjou Moumouni PF, Cao S, Asada M, Wang G, Gao Y, Guo H, Li J, Vudriko P, Efstratiou A, Ringo AE, Lee
SH, Hakimi H, Masatani T, Sunaga F, Kawazu SI, Yamagishi J, Jia L, Inoue N, Xuan X: “Identification andcharacterization of interchangeable cross-species functional promoters between Babesia gibsoni and Babesia bovis”,
Ticks Tick Borne Dis, 9(2):330-333 (2018) i)
60) Bwalya P, Yamaguchi T, Mulundu G, Nakajima C, Mbulo G, Solo ES, Fukushima Y, Kasakwa K, Suzuki Y: “Genotypiccharacterization of pyrazinamide resistance in Mycobacterium tuberculosis isolated from Lusaka, Zambia.”
Tuberculosis,109:117-122 (2018) i)
61) Habeenzu C, Nakajima C, Solo E, Bwalya P, Kajino K, Miller M, Kurosawa Y, Mudenda V, Kasonka L, Suzuki Y,
Matsuba T: “Evaluation of in-house loop-mediated isothermal amplification for the diagnosis of tuberculosis incomparison with GeneXpert MTB/RIF.” J Infect Dev Ctries, 11(6):440-444 (2017) i)
62) Nguyen LT, Nakaishi K, Motojima K, Ohkawara A, Minato E, Maruyama J, Hiono T, Matsuno K, Okamatsu M, Kimura
T, Takada A, Kida H, Sakoda Y: “Rapid and broad detection of H5 hemagglutinin by an immunochromatographic kit
using novel monoclonal antibody against highly pathogenic avian influenza virus belonging to the genetic clade
2.3.4.4.”, PLoS One, 12(8), e0182228 (2017) i)
63) Hiono T, Okamatsu M, Matsuno K, Haga A, Iwata R, Nguyen LT, Suzuki M, Kikutani Y, Kida H, Onuma M, Sakoda
Y: “Characterization of H5N6 highly pathogenic avian influenza viruses isolated from wild and captive birds in thewinter season of 2016-2017 in northern Japan”, Microbiol Immunol, 61(9), 387-397(2017) i) ii)
64) Ohkawara A, Okamatsu M, Ozawa M, Chu DH, Nguyen LT, Hiono T, Matsuno K, Kida H, Sakoda Y: “Antigenic
diversity of H5 highly pathogenic avian influenza viruses of clade 2.3.4.4 isolated in Asia”, Microbiol Immunol, 61(5),149-158 (2017) i)

96

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65) Chu DH, Stevenson MA, Nguyen LV, Isoda N, Firestone SM, Nguyen TN, Nguyen LT, Matsuno K, Okamatsu M,
Kida H, Sakoda Y: “A cross-sectional study to quantify the prevalence of avian influenza viruses in poultry atintervention and non-intervention live bird markets in central Vietnam, 2014”, Transbound Emerg Dis, 64(6), 1991999(2017) i)
66) Nguyen LT, Nishi T, Shichinohe S, Chu DH, Hiono T, Matsuno K, Okamatsu M, Kida H, Sakoda Y: “Selection of
antigenic variants of an H5N1 highly pathogenic avian influenza virus in vaccinated chickens”, Virology, 10, 252261(2017) i)
67) Enkhbold B, Shatar M, Wakamori S, Tamura T, Hiono T, Matsuno K, Okamatsu M, Umemura T, Damdinjav B, Sakoda
Y : “Genetic and virulence characterization of classical swine fever viruses isolated in Mongolia from 2007 to 2015”,
Virus Genes, 53(3), 418-425(2017) i) ii)
68) Gulyaeva M, Sharshov K, Suzuki M, Sobolev I, Sakoda Y, Alekseev A, Sivay M, Shestopalova L, Shchelkanov M,
Shestopalov A : “Genetic characterization of an H2N2 influenza virus isolated from a muskrat in Western Siberia”, J
Vet Med Sci, 79(8), 1461-1465(2017) i)
69) Simulundu E, Lubaba CH, van Heerden J, Kajihara M, Mataa L, Chambaro HM, Sinkala Y, Munjita SM, Munang'andu
HM, Nalubamba KS, Samui K, Pandey GS, Takada A, Mweene AS: “The Epidemiology of African Swine Fever in"Nonendemic" Regions of Zambia (1989-2015): Implications for Disease Prevention and Control”, Viruses, 9(9).pii,
E236 review (2017) i)
70) Simulundu E, Mtine N, Kapalamula TF, Kajihara M, Qiu Y, Ngoma J, Zulu V, Kwenda G, Chisanga C, Phiri
IK, Takada A, Mweene AS: “ Genetic characterization of orf virus associated with an outbreak of severe orf in goatsat a farm in Lusaka, Zambia(2015)”, Arch Virol, 162(8), 2363-2367(2017) i) ii)
71) Pandey GS, Simulundu E, Mwiinga D, Samui KL, Mweene AS, Kajihara M, Mangani A, Mwenda R, Ndebe J, Konnai
S, Takada A: “Clinical and subclinical bovine leukemia virus infection in a dairy cattle herd in Zambia”, Arch Virol,
162(4), 1051-1056 (2017) i)
72) Manzoor R, Igarashi M, Takada A, “Influenza A Virus M2 Protein: Roles from Ingress to Egress”, Int J Mol Sci,
18(12) (2017) i)
73) Kondoh T, Manzoor R, Nao N, Maruyama J, Furuyama W, Miyamoto H, Shigeno A, Kuroda M, Matsuno K, Fujikura
D, Kajihara M, Yoshida R, Igarashi M, Takada A : “Putative endogenous filovirus VP35-like protein potentiallyfunctions as an IFN antagonist but not a polymerase cofactor”, PLoS One, 12(10), e0186450 (2017) i)
74) Ogawa H, Kajihara M, Nao N, Shigeno A, Fujikura D, Hang'ombe BM, Mweene AS, Mutemwa A, Squarre D, Yamada
M, Higashi H, Sawa H, Takada A: “Characterization of a Novel Bat Adenovirus Isolated from Straw-Colored Fruit Bat(Eidolon helvum)”, Viruses, 9(12) (2017) i) ii)
75) Utrarachkij F, Nakajima C, Changkwanyeun R, Siripanichgon K, Kongsoi S, Pornruangwong S, Changkaew K,
Tsunoda R, Tamura Y, Suthienkul O, Suzuki Y: “Quinolone Resistance Determinants of Clinical Salmonella Enteritidis
in Thailand”, Microb Drug Resist,23(7), 885-894 (2017) i)
76) Zhao J, Matsuba T, Zhang X, Leano S, Nakajima C, Chagan-Yasutan H, Telan EF, Suzuki Y, Hattori T: “Comparisonof antibody responses against Mycobacterium tuberculosis antigen Rv0679c in tuberculosis patients from the endemic
and non-endemic regions of the Beijing genotype: a case control study”, BMC Infect Dis, 17(1), 344 (2017) i) ii)

97

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77) Pan XL, Zhang CL, Nakajima C, Fu J, Shao CX, Zhao LN, Cui JY, Jiao N, Fan CL, Suzuki Y, Hattori T, Li D, Ling
H: “A quantitative and efficient approach to select MIRU-VNTR loci based on accumulation of the percentage
differences of strains for discriminating divergent Mycobacterium tuberculosis sublineages”, Emerg Microbes Infect,
6(7), e68 (2017) i)
78) Yano H, Iwamoto T, Nishiuchi Y, Nakajima C, Starkova DA, Mokrousov I, Narvskaya O, Yoshida S, Arikawa K,
Nakanishi N, Osaki K, Nakagawa I, Ato M, Suzuki Y, Maruyama F: “Population Structure and Local Adaptation of
MAC Lung Disease Agent Mycobacterium avium subsp. hominissuis”, Genome Biol Evol, 9(9), 2403-2417 (2017) i)
ii)
79) Rahim Z, Thapa J, Fukushima Y, van der Zanden AG, Gordon SV, Suzuki Y, Nakajima C : “Tuberculosis Caused by
Mycobacterium orygis in Dairy Cattle and Captured Monkeys in Bangladesh: a New Scenario of Tuberculosis in South
Asia”, Transbound Emerg Dis, 64(6), 1965-1969(2017) i) ii)
80) Shah Y, Maharjan B, Thapa J, Poudel A, Diab HM, Pandey BD, Solo ES, Isoda N, Suzuki Y, Nakajima C : “Highdiversity of multidrug-resistant Mycobacterium tuberculosis Central Asian Strain isolates in Nepal”, Int J Infect Dis,63, 13-20 (2017) i) ii)
81) Bortey-Sam N, Ikenaka Y, Akoto O, Nakayama SMM, Asante KA, Baidoo E, Obirikorang C, Saengtienchai A, Isoda
N, Nimako C, Mizukawa H, Ishizuka M: “Oxidative stress and respiratory symptoms due to human exposure topolycyclic aromatic hydrocarbons (PAHs) in Kumasi, Ghana”, Environ Pollut, 228, 311-320 (2017) i) ii)
82) Reteng P, Vrisca V, Sukarno I, Djarkoni IH, Kalangi JA, Jacobs GE, Runtuwene LR, Eshita Y, Maeda R, Suzuki Y,
Mongan AE, Warouw SM, Yamagishi J, Tuda J: “Genetic polymorphisms in Plasmodium falciparum chloroquine
resistance genes, pfcrt and pfmdr1, in North Sulawesi, Indonesia”, BMC Res Notes, 10(1), 147 (2017) i)
83) Yamagishi J, Runtuwene LR, Hayashida K, Mongan AE, Thi LAN, Thuy LN, Nhat CN, Limkittikul K, Sirivichayakul
C, Sathirapongsasuti N, Frith M, Makalowski W, Eshita Y, Sugano S, Suzuki Y: “Serotyping dengue virus withisothermal amplification and a portable sequencer”, Sci Rep, 7(1), 3510 (2017) i)
84) Imai K, Tarumoto N, Misawa K, Runtuwene LR, Sakai J, Hayashida K, Eshita Y, Maeda R, Tuda J, Murakami T,
Maesaki S, Suzuki Y, Yamagishi J, Maeda T: “A novel diagnostic method for malaria using loop-mediated isothermal
amplification (LAMP) and MinION™ nanopore sequencer”, BMC Infect Dis, 17(1), 621 (2017) i)
85) Nakayama M, Itoh Y, Shichinohe S, Nakabayashi R, Ishigaki H, Sakoda Y, Le QM, Kawaoka Y, Kida H, Ogasawara
K: “Potential risk of repeated nasal vaccination that induces allergic reaction with mucosal IgE and airway eosinophilic
infiltration in cynomolgus macaques infected with H5N1 highly pathogenic avian influenza virus”, Vaccine, 35(7),1008-1017(2017) i) ii)
86) Nao N, Yamagishi J, Miyamoto H, Igarashi M, Manzoor R, Ohnuma A, Tsuda Y, Furuyama W, Shigeno A, Kajihara
M, Kishida N, Yoshida R, Takada A: “Genetic Predisposition To Acquire a Polybasic Cleavage Site for Highly
Pathogenic Avian Influenza Virus Hemagglutinin”, MBio, 8(1). pii, e02298-16 (2017) i)
87) Nakao R, Matsuno K, Qiu Y, Maruyama J, Eguchi N, Nao N, Kajihara M, Yoshii K, SawaH, Takada A, Sugimoto C:“Putative RNA viral sequences detected in an Ixodes scapularis-derived cell line”, Ticks Tick Borne Dis, 8(1), 103111(2017) i)
88) Gonzalez G, Sasaki M, Burkitt-Gray L, Kamiya T, Tsuji NM, Sawa H, Ito K: “An optimistic protein assembly fromsequence reads salvaged an uncharacterized segment of mouse picobirnavirus”, Sci Rep, 7, 40447(2017) i)

98

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89) Tun T, Aye KS, Nyunt WW, Crump JA, Nakajima C, Suzuki Y, Thinn KK, Cook GM, Aung HL: “Genotypic diversityof Mycobacterium tuberculosis strains in Myanmar”, Infect Dis (Lond), 49(3), 237-239 (2017) i)
90) Matsuno K, Orba Y, Maede-White K, Scott D, Feldmann F, Liang M, Ebihara H: “Animal Models of Emerging TickBorne Phleboviruses: Determining Target Cells in a Lethal Model of SFTSV Infection”, Front Microbiol, 8, 104(2017) i)
91) Hayashida K, Kajino K, Simukoko H, Simuunza M, Ndebe J, Chota A, Namangala B, Sugimoto C: “Direct detectionof falciparum and non-falciparum malaria DNA from a drop of blood with high sensitivity by the dried-LAMP system”,
Parasit Vectors, 10(1), 26 (2017) i)
92) Chu DH, Okamatsu M, Matsuno K, Hiono T, Ogasawara K, Nguyen LT, Van Nguyen L, Nguyen TN, Nguyen TT,
Van Pham D, Nguyen DH, Nguyen TD, To TL, Van Nguyen H, Kida H, Sakoda Y : “Genetic and antigenic
characterization of H5, H6 and H9 avian influenza viruses circulating in live bird markets with intervention in thecenter part of Vietnam”, Vet Microbiol,192,194-203(2016) i)
93) Yamada T, Horimoto H, Kameyama T, Hayakawa S, Yamato H, Dazai M, Takada A, Kida H, Bott D, Zhou AC, Hutin
D, Watts TH, Asaka M, Matthews J, Takaoka A: “Constitutive aryl hydrocarbon receptor signaling constrains type I
interferon-mediated antiviral innate defense”, Nat Immunol, 17(6), 687-94 (2016) i)
94) Simulundu E, Mweene AS, Changula K, Monze M, Chizema E, Mwaba P, Takada A, Ippolito G, Kasolo F, Zumla A,
Bates M: “Lujo viral hemorrhagic fever: considering diagnostic capacity and preparedness in the wake of recent Ebola
and Zika virus outbreaks”, Rev Med Virol, 26(6), 446-454(2016) i)
95) Yoshida R, Muramatsu S, Akita H, Saito Y, Kuwahara M, Kato D, Changula K, Miyamoto H, Kajihara M, Manzoor
R, Furuyama W, Marzi A, Feldmann H, Mweene A, Masumu J, Kapeteshi J, Muyembe-Tamfum JJ, Takada A :“Development of an Immunochromatography Assay (QuickNavi-Ebola) to Detect Multiple Species of Ebolaviruses”,
J Infect Dis, 214(suppl3), S185-S191(2016) i)
96) Furuyama W, Marzi A, Carmody AB, Maruyama J, Kuroda M, Miyamoto H, Nanbo A, Manzoor R, Yoshida R,
Igarashi M, Feldmann H, Takada A: “Fcγ-receptor IIa-mediated Src Signaling Pathway Is Essential for the AntibodyDependent Enhancement of Ebola Virus Infection”, PLoS Pathog, 12(12), e1006139 (2016) i)
97) Kouwaki T, Fukushima Y, Daito T, Sanada T, Yamamoto N, Mifsud EJ, Leong CR, Tsukiyama-Kohara K, Kohara M,
Matsumoto M, Seya T, Oshiumi H: “Extracellular Vesicles Including Exosomes Regulate Innate Immune Responses
to Hepatitis B Virus Infection”, Front Immunol,7, 335(2016) ) i) ii)
98) Sasaki M, Orba Y, Sasaki S, Gonzalez G, Ishii A, Hang’ombe BM, Mweene AS, Ito K, Sawa H: “Multi-reassortant
G3P[3] group A rotavirus in a horseshoe bat in Zambia”, J Gen Virol, 97(10), 2488-2493 (2016) i) ii)
99) Sasaki M, Gonzalez G, Wada Y, Setiyono A, Handharyani E, Rahmadani I, Taha S, Adiani S, Latief M, Kholilullah
ZA, Subangkit M, Kobayashi S, Nakamura I, Kimura T, Orba Y, Ito K, Sawa H : “Divergent bufavirus harboured inmegabats represents a new lineage of parvoviruses”, Sci Rep, 6, 24257(2016) i)
100)

Villanueva MA, Mingala CN, Balbin MM, Nakajima C, Isoda N, Suzuki Y*, Koizumi N: “Molecularepidemiology of pathogenic Leptospira spp. among large ruminants in the Philippines.” J Vet Med Sci, 78(11):164955 (2016) i)
101)

Chagan-Yasutan H, Chen Y, Lacuesta TL, Leano PS, Iwasaki H, Hanan F, Taurustiati D, Ohmoto Y, Ashino Y,

Saitoh H, Kiyomoto H, Suzuki Y, Telan FO, Hattori T: “Urine Levels of Defensin α1 Reflect Kidney Injury in
Leptospirosis Patients”, Int J Mol Sci, 17(10), 1637(2016) i) ii)

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102)

Chishimba K, Hang’ombe BM, Muzandu K, Mshana SE, Matee MI, Nakajima C, Suzuki Y : “Detection ofExtended-Spectrum Beta-Lactamase-Producing Escherichia coli in Market-Ready Chickens in Zambia”, Int J
Microbiol, 2016, 5275724 (2016) i) ii)
103)

Utrarachkij F, Nakajima C, Siripanichgon K, Changkaew K, Thongpanich Y, Pornraungwong S,

Suthienkul O, Suzuki Y: “Genetic diversity and antimicrobial resistance pattern of Salmonella enterica serovar
enteritidis clinical isolates in Thailand”, J Infect Chemother, 22,209-15 (2016) i) ii)
104)

Changkwanyeun R, Yamaguchi T, Kongsoi S, Changkaew K, Yokoyama K, Kim H, Suthienkul O, Usui M,

Tamura Y, Nakajima C, Suzuki Y: “ Impact of mutations in DNA gyrase genes on quinolone resistance inCampylobacter jejuni”, Drug Test Anal, 8(10), 1071-1076 (2016) i)
105)

Paudel S, Villanueva MA, Mikota SK, Nakajima C, Gairhe KP, Subedi S, Rayamajhi N, Sashika M, Shimozuru

M, Matsuba T, Suzuki Y, Tsubota T: “Development and evaluation of an interferon-γ release assay (IGRA) in Asianelephants (Elephas maximus)”, J Vet Med Sci, 78(7), 1171-21 (2016) i)
106)

Kongsoi S, Changkwanyeun R, Yokoyama K, Nakajima C, Changkaew K, Suthienkul O, Suzuki Y: “Amino acidsubstitutions in GyrA affect quinolone susceptibility in Salmonella typhimurium”, Drug Test Anal, 8(10), 1065-1070(2016) i) ii)
107)

Nakao R, Jongejan F, Sugimoto C : “Draft Genome Sequences of Three Strains of Ehrlichia ruminantium, a Tick-

Borne Pathogen of Ruminants, Isolated from Zimbabwe, The Gambia, and Ghana”, Genome Announc, 4(3), e0045316 (2016) i)
108)

Nakao R, Abe T, Funayama S, Sugimoto C : “Horizontally Transferred Genetic Elements in the Tsetse Fly

Genome: An Alignment-Free Clustering Approach Using Batch Learning Self-Organising Map (BLSOM)”, Biomed
Res Int, 2016, 3164624(2016) i)
109)

Suganuma K, Sarwono AE, Mitsuhashi S, Jąkalski M, Okada T, Nthatisi M, Yamagishi J, Ubukata M, Inoue N:“Mycophenolic Acid and Its Derivatives as Potential Chemotherapeutic Agents Targeting Inosine Monophosphate
Dehydrogenase in Trypanosoma congolense”, Antimicrob Agents Chemother, 60(7), 4391-3(2016) i)
110)

Hiono T, Okamatsu M, Igarashi M, McBride R, de Vries RP, Peng W, Paulson JC, Sakoda Y, Kida H: “Aminoacid residues at positions 222 and 227 of the hemagglutinin together with the neuraminidase determine binding of H5
avian influenza viruses to sialyl Lewis X”, Arch Virol, 161, 307-16, (2016) i）
111)

Furuyama W, Marzi A, Nanbo A, Haddock E, Maruyama J, Miyamoto H, Igarashi M, Yoshida R, Noyori O,

Feldmann H, Takada A: “Discovery of an antibody for pan-ebolavirus therapy”, Sci Rep, 6 ,20514 (2016) i）
112)

Maruyama J, Nao N, Miyamoto H, Maeda K, Ogawa H, Yoshida R, Igarashi M, Takada A: “Characterization of

the glycoproteins of bat-derived influenza viruses”, Virology, 488, 43-50 (2016) i）
113)

Khin Saw Aye, Nakajima C, Yamaguchi T, Min Min Win, Mu Mu Shwe, Aye Aye Win, Thandar Lwin, Wint Wint

Nyunt, Ti Ti, Suzuki Y : “Genotypic characterization of multi-drug-resistant Mycobacterium tuberculosis isolates in
Myanmar.”, J Infect Chemother, 22(3),174-9 (2016) i) ii)
114)

Diab HM, Nakajima C, Kotb SA, Mokhtar A, Khder NFM, Abdelaal ASA, Hegazy A, Poudel A, Shah Y, Suzuki

Y : “First insight into the genetic population structure of Mycobacterium tuberculosis isolated from pulmonary
tuberculosis patients in Egypt.”, Tuberculosis, 96,13-20 (2016) i) ii)

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Thapa J, Paudel S, Sadaula A, Shah Y, Maharjan B, Kaufman GE, McCauley D, Gairhe KP, Tsubota T, Suzuki Y,

Nakajima C: “Mycobacterium orygis–associated tuberculosis in free-ranging rhinoceros, Nepal,2015”, Emerg InfectDis, 22(3): 570–2 (2016) i)
116)

Villanueva MA, Mingala CN, Gloriani NG, Yanagihara Y, Isoda N, Nakajima C, Suzuki Y, Koizumi N:“Serological investigation of Leptospira infection and its circulation in one intensive-type water buffalo farm in thePhilippines”, Jpn J Vet Res, 64(1), 15-24 (2016) i)
117)

Qiu Y, Nakao R, Thu MJ, Akter S, Alam MZ, Kato S, Katakura K, Sugimoto C: “Molecular evidence of spotted

fever group Rickettsiae and Anaplasmataceae from ticks and stray dogs in Bangladesh”, Parasitol Res, 115(3), 94955 (2016) i)
118)

Tamura T, Ruggli N, Nagashima N, Okamatsu M, Igarashi M, Mine J, Hofmann MA, Liniger M, SummerfieldA, Kida H, Sakoda Y: “Intracellular membrane association of the N-terminal domain of classical swine fever virus
NS4B determines viral genome replication and virulence”, J Gen Virol, 96(9), 2623-35 (2015) i)
119)

Hiono T, Ohkawara A, Ogasawara K, Okamatsu M, Tamura T, Chu DH, Suzuki M, Kuribayashi S, Shichinohe

S, Takada A, Ogawa H, Yoshida R, Miyamoto H, Nao N, Furuyama W, Maruyama J, Eguchi N, Ulziibat G, Enkhbold
B, Shatar M, Jargalsaikhan T, Byambadorj S, Damdinjav B, Sakoda Y, Kida H : “ Genetic and antigenic
characterization of H5 and H7 influenza viruses isolated from migratory water birds in Hokkaido, Japan and Mongolia
from 2010 to 2014”, Virus Genes, 51(1), 57-68 (2015) i)
120)

Mine J, Tamura T, Mitsuhashi K, Okamatsu M, Parchariyanon S, Pinyochon W, Ruggli N, Tratschin JD, Kida

H, Sakoda Y : “The N-terminal domain of Npro of classical swine fever virus determines its stability and regulates
type I IFN production”, J Gen Virol, 96(Pt 7), 1746-56 (2015) i)
121)

Nao N, Kajihara M, Manzoor R, Maruyama J, Yoshida R, Muramatsu M, Miyamoto H, Igarashi M,

Eguchi N,

Sato M, Kondoh T, Okamatsu M, Sakoda Y, Kida H, Takada A: “A single amino acid in the M1 protein responsible
for the different pathogenic potentials of H5N1 highly pathogenic avian influenza virus strains”, PLoS One, 10(9),e0137989 (2015) i)
122)

Ogawa H, Koizumi N, Ohnuma A, Mutemwa A, Hang’ombe BM, Mweene AS, Takada A, Sugimoto C, Suzuki

Y, Kida H, Sawa H: “Molecular epidemiology of pathogenic Leptospira spp. in the straw-colored fruit bat (Eidolon
helvum) migrating to Zambia from the Democratic Republic of Congo”, Infect Genet Evol, 32, 143-7 (2015) i) ii)
123)

Ogawa H, Miyamoto H, Nakayama E, Yoshida R, Nakamura I, Sawa H, Ishii A, Thomas Y, Nakagawa

E, Matsuno K, Kajihara M, Maruyama J, Nao N, Muramatsu M, Kuroda M, Simulundu E, Changula K, Hang’ombe B,
Namangala B, Nambota A, Katampi J, Igarashi M, Ito K, Feldmann H, Sugimoto C, Moonga L, Mweene A, Takada
A: “Seroepidemiological prevalence of multiple species of filoviruses in fruit bats (Eidolon helvum) migrating in
Africa”, J Infect Dis, 212 Suppl 2, S101-8 (2015) i) ii)
124)

Kuroda M, Fujikura D, Nanbo A, Marzi A, Noyori O, Kajihara M, Maruyama J, Matsuno K, Miyamoto H,

Yoshida R, Feldmann H, Takada A : “Interaction between TIM-1 and NPC1 is important for cellular entry of ebola
virus”, J Virol, 89(12), 6481-93 (2015) i)
125)

Sasaki M, Orba Y, Anindita PD, Ishii A, Ueno K, Hang’ombe BM, Mweene AS, Ito K, Sawa H: “Distinct lineagesof bufavirus in wild shrews and nonhuman primates.”, Emerg Infect Dis, ;21(7),1230-3(2015) ii)

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126)

Anindita PD, Sasaki M, Setiyono A, Handharyani E, Orba Y, Kobayashi S, Rahmadani I, Taha S, Adiani S,

Subangkit M, Nakamura I, Sawa H, Kimura T: “Detection of coronavirus genomes in Moluccan naked-backed fruitbats in Indonesia”, Arch Virol,160(4), 1113-8 (2015) i) ii)
127)

Kongsoi S, Yokoyama K, Suprasert A, Utrarachkij F, Nakajima C, Suthienkul O, Suzuki Y: “Characterization of

Salmonella Typhimurium DNA gyrase as a target of quinolones”, Drug Test Anal, 7(8), 714-20 (2015) i)
128)

Changkwanyeun R, Usui M, Kongsoi S, Yokoyama K, Kim H, Suthienkul O, Changkaew K, Nakajima C,

Tamura Y, Suzuki Y: “Characterization of Campylobacter jejuni DNA gyrase as the target of quinolones”, J InfectChemother, 21(8), 604-9 (2015) i)
129)

Changkaew K, Intarapuk A, Utrarachkij F, Nakajima C, Suthienkul O, Suzuki Y : “Antimicrobial resistance,

extended-spectrum β-lactamase productivity, and class 1 integrons in Escherichia coli from healthy swine”, J Food
Prot, 78(8), 1442-50 (2015) i) ii)
130)

Kobayashi S, Sasaki M, Nakao R, Setiyono A, Handharyani E, Orba Y, Rahmadani I, Taha S, Adiani S, Subangkit

M, Nakamura I, Kimura T, Sawa H : “ Detection of novel polyomaviruses in fruit bats in Indonesia”, Arch Virol,160(4),1075-82 (2015) i)
131)

Ogawa H, Fujikura D, Ohnuma M, Ohnishi N, Hang'ombe BM, Mimuro H, Ezaki T, Mweene AS, Higashi H :“A novel multiplex PCR discriminates Bacillus anthracis and its genetically related strains from other Bacillus cereus
group species”, PLoS One, 10(3), e0122004(2015) i) ii)
132)

Orba Y, Sasaki M, Yamaguchi H, Ishii A, Thomas Y, Hang’ombe BM, Mweene AS, Morikawa S, Saijo M, Sawa

H: “Orthopoxvirus infection among wildlife in Zambia”, J Gen Virol, 96(Pt 2), 390-4 (2015) i)
133)

Sasaki M, Orba Y, Ueno K, Ishii A, Moonga L, Hang’ombe BM, Mweene AS, Ito K, Sawa H,: “Metagenomic

analysis of shrew enteric virome reveals novel viruses related to human stool-associated viruses”, J Gen Virol, 96(Pt2), 440-52 (2015) i)Jąkalski M, Wakaguri H, Kischka TG, Nishikawa Y, Kawazu SI, Matsubayashi M, Kawahara F, Tsuji N, Cao S,

134)

Sunaga F, Xuan X, Okubo K, Igarashi I, Tuda J, Mongan AE, Eshita Y, Maeda R, Makałowski W, Suzuki Y, Yamagishi
J : “ DB-AT: a 2015 update to the Full-parasites Database brings a multitude of new transcriptomic data for
apicomplexan parasites”, Nucleic Acids Res, 43 (Database issue), D631-6 (2015) i)
135)

Kuroda M, Fujikura D, Noyori O, Kajihara M, Maruyama J, Miyamoto H, Yoshida R, Takada A: “Apolymorphism of the TIM-1 IgV domain: Implications for the susceptibility to filovirus Infection”, Biochem Biophys
Res Commun, 455(3-4), 223-228 (2014) i)
2

Other original papers：#100
i) Papers where "GI-CoRE" is stated as an affiliated institutionii) Papers which mention "Hokkaido University" in the acknowledgements

1) Goto S, Konnai S, Hirano Y, Kohara J, Okagawa T, Maekawa N, Sajiki Y, Watari K, Minato E, Kobayashi A,
Gondaira S, Higuchi H, Koiwa M, Tajima M, Taguchi E, Uemura R, Yamada S, Kaneko MK, Kato Y, Yamamoto K,
Toda M, Suzuki Y, Murata S, Ohashi K: “Upregulation of PD-L1 Expression by Prostaglandin E2 and theEnhancement of IFN-γ by Anti-PD-L1 Antibody Combined With a COX-2 Inhibitor in Mycoplasma bovis Infection”,
Front Vet Sci, 7:12 (2020) i)

102

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,2) Ohkoshi Y, Sato T, Murabayashi H, Sakai K, Takakuwa Y, Fukushima Y, Nakajima C, Suzuki Y, Yokota SI:“Campylobacter upsaliensis isolated from a giant hepatic cyst”, J Infect Chemother. 2020 Mar 18. pii: S1341321X(20)30063-5. doi: 10.1016/j.jiac.2020.02.015. [Epub ahead of print] (2020) i) ii)
3) Oe C, Hayashi H, Hirata K, Kawaji K, Hashima F, Sasano M, Furuichi M, Usui E, Katsumi M, Suzuki Y, Nakajima C,
Kaku M, Kodama EN*: “Pyrimidine Analogues as a New Class of Gram-Positive Antibiotics, Mainly Targeting
Thymineless-Death Related Proteins”, ACS Infect Dis. 2019 Oct 8. doi: 10.1021/acsinfecdis.9b00305. [Epub aheadof print] (2019)4) Isoda N, Baba K, Ito S, Ito M, Sakoda Y, Makita K: "Dynamics of Classical Swine Fever Spread in Wild Boar in 20182019, Japan", Pathogens, 9(2) (2020) i)
5) Suzuki Y, Sato T, Fukushima Y, Nakajima C, Takahashi S, Yokota SI: "Contribution of beta-lactamase and efflux
pump overproduction to tazobactam-piperacillin resistance in clinical isolates of Escherichia coli", Int J Antimicrob
Agents:105919(2020) i)
6) Yamagishi J, Hayashida K, Matsuo J, Okubo T, Kuroda M, Nagai H, Sekizuka T, Yamaguchi H, Sugimoto C:"Complete genome and bimodal genomic structure of the amoebal symbiont Neochlamydia strain S13 revealed byultra-long reads obtained from MinION", J Hum Genet, 65(1):41-48(2020). i)7) Kobayashi S, Yoshii K, Phongphaew W, Muto M, Hirano M, Orba Y, Sawa H, Kariwa H: "West Nile virus capsid
protein inhibits autophagy by AMP-activated protein kinase degradation in neurological disease development", PLoS
Pathog, 16(1):e1008238(2020) i) ii)
8) Honda H, Sato T, Shinagawa M, Fukushima Y, Nakajima C, Suzuki Y, Kuronuma K, Takahashi S, Takahashi H,
Yokota SI: "In vitro Derivation of Fluoroquinolone-resistant Mutants from Multiple Lineages of Haemophilus
influenzae and Identification of Mutations Associated with Fluoroquinolone Resistance", Antimicrob Agents
Chemother, 64(2):e01500-19 (2020). i) ii)
9) Sakaguchi S, Shintani S, Kamio K, Sekiya A, Kato S, Muroi Y, Horiuchi M, Furuoka H:"Selective neuronalvulnerability is involved in cerebellar lesions of Guinea pigs infected with bovine spongiform encephalopathy (BSE)prions: Immunohistochemical and electron microscopic investigations", Neuropathology, 40(2):167-179 (2020).
10) Muramatsu Y, Haraya N, Horie K, Uchida L, Kooriyama T, Suzuki A, Horiuchi M: “Bergeyella zoohelcum isolated
from oral cavities of therapy dogs”, Zoonoses Public Health, 66(8): 936-942 (2019)11) Hagiwara K, Sato Y, Yamakawa Y, Hara H, Tobiume M, Okemoto-Nakamura Y, Sata T, Horiuchi M, Shibata H,
Ono F: “Tracking and clarifying differential traits of classical- and atypical L-type bovine spongiform encephalopathy
prions after transmission from cattle to cynomolgus monkeys”. PLoS One, 14(5): e0216807 (2019)12) Watanabe T, Suzuki N, Tomonaga K, Sawa H, Matsuura Y, Kawaguchi Y, Takahashi H, Nagasaki K, Kawaoka Y: “Neovirology: The raison d'etre of viruses”, Virus Res Dec, 274:197751 (2019)13) Hiyama Y, Takahashi S, Sato T, Shinagawa M, Fukushima Y, Nakajima C, Suzuki Y, Masumori N, Yokota SI:"Evaluation of Susceptibilities to Carbapenems and Faropenem Against Cephalosporin-Resistant Neisseria
gonorrhoeae Clinical Isolates with penA Mosaic Alleles", Microb Drug Resist, 25(3):427-433(2019) i)
14) Isoda N, Asano A, Ichijo M, Ohno H, Sato K, Okamoto H, Nakao S, Kato H, Saito K, Ito N, Usui A, Takayama H,
Sakoda Y: "Assessment of the cost effectiveness of compulsory testing of introduced animals and bulk tank milk testingfor bovine viral diarrhea in Japan", J Vet Med Sci, 81(4):577-585(2019) i)

103

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15) Kobayashi A, Iwasaki Y, Takao M, Saito Y, Iwaki T, Qi Z, Torimoto R, Shimazaki T, Munesue Y, Isoda N, Sawa H,
Aoshima K, Kimura T, Kondo H, Mohri S, Kitamoto T: "A Novel Combination of Prion Strain Co-Occurrence inPatients with Sporadic Creutzfeldt-Jakob Disease", Am J Pathol, 189(6):1276-1283(2019) i)
16) Matsubayashi M, Yamaguchi H, Hatta T, Kawahara F, Hatabu T, Iseki H, Yamagishi J, Isobe T, Teramoto I, Kaneko
A, Kita K, Tsuji N, Sasai K: "Transitions in morphological forms and rapid development of the asexual schizonts ofEimeria tenella through serial passaging in chicks", Infect Genet Evol:103993(2019) i)
17) Morimoto A, Uchida K, Chambers JK, Sato K, Hong J, Sanjoba C, Matsumoto Y, Yamagishi J, Goto Y:"Hemophagocytosis induced by Leishmania donovani infection is beneficial to parasite survival within macrophages",
PLoS Negl Trop Dis, 13(11) (2019). i)
18) Park JH, Yamaguchi T, Ouchi Y, Koide K, Mori S, Kim H, Mukai T, Nakajima C, Suzuki Y: "WQ-3810 inhibits DNA
gyrase activity in ofloxacin-resistant Mycobacterium leprae", J Infect Chemother, 12(19):30330-30337(2019). i)
19) Sajiki Y, Konnai S, Okagawa T, Nishimori A, Maekawa N, Goto S, Watari K, Minato E, Kobayashi A, Kohara J,
Yamada S, Kaneko M, Kato Y, Takahashi H, Terasaki N, Takeda A, Yamamoto K, Toda M, Suzuki Y, Murata S,
Ohashi K: "Prostaglandin E2-induced immune exhaustion and enhancement of antiviral effects by anti-PD-L1 antibody
combined with COX-2 inhibitor in bovine leukemia virus infection", J Immunol, 203(5):1313-1324(2019) i)
20) Sawada K, Suzuki A, Yamasaki T, Iwamaru Y, Matsuura Y, Miyazawa K, Masujin K, Atarashi R, Horiuchi M:"Estimation of prion infectivity in tissues of cattle infected with atypical BSE by real time-quaking induced conversion
assay", J Vet Med Sci, 81(6):846-850(2019). i) ii)
21) Suzuki A, Yamasaki T, Hasebe R, Horiuchi M: "Enhancement of binding avidity by bivalent binding enables PrPScspecific detection by anti-PrP monoclonal antibody 132", PLoS One, 14(6) (2019). i)
22) Tamura T, Igarashi M, Enkhbold B, Suzuki T, Okamatsu M, Ono C, Mori H, Izumi T, Sato A, Fauzyah Y, Okamoto
T, Sakoda Y, Fukuhara T, Matsuura Y: "In vivo dynamics of reporter Flaviviridae viruses", J Virol, 93(22) (2019) i)
ii)
23) Tani H, Kawachi K, Kimura M, Taniguchi S, Shimojima M, Fukushi S, Igarashi M, Morikawa S, Saijo M:"Identification of the amino acid residue important for fusion of severe fever with thrombocytopenia syndrome virus
glycoprotein", Virology, 535:102-110(2019) i)
24) Watari K, Konnai S, Maekawa N, Okagawa T, Suzuki Y, Murata S, Ohashi K: "Immune inhibitory function of bovine
CTLA-4 and the effects of its blockade in IFN-γ production", BMC Vet Res, 15(1):380 (2019). i)
25) Usui M, Kajino A, Kon M, Fukuda A, Sato T, Shirakawa T, Kawanishi M, Harada K, Nakajima C, Suzuki Y, Tamura
Y: “Prevalence of 16S rRNA methylases in Gram-negative bacteria derived from companion animals and livestock inJapan”, J Vet Med Sci, 81(6):874-878 (2019)26) Shibata A, Harada R, Okamatsu M, Matsuno K, Arita T, Suzuki Y, Shirakura M, Odagiri T, Takemae N, Uchida Y,
Saito T, Sakoda Y, Osaka H: "Characterization of a novel reassortant H7N3 highly pathogenic avian influenza virus
isolated from a poultry meat product taken on a passenger flight to Japan", J Vet Med Sci, 81(3):444-448(2019) i)
27) Sun L, Kono N, Toh H, Xue H, Sano K, Suzuki T, Ainai A, Orba Y, Yamagishi J, Hasegawa H, Takahashi Y, Itamura
S, Ohnishi K: "Identification of Mouse and Human Antibody Repertoires by Next-Generation Sequencing", J Vis Exp,
(145)(2019) i)ii)

104

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28) Fujisawa S, Konnai S, Okagawa T, Maekawa N, Tanaka A, Suzuki Y, Murata S, Ohashi K: “Effects of Bovine Tumor
Necrosis Factor Alpha Decoy Receptors on Cell Death and Inflammatory Cytokine Kinetics: Potential for Bovine
Inflammation Therapy”, BMC Vet Res, 15(1):68 (2019) i)
29) Taniguchi K, Ando Y, Nobori H, Toba S, Noshi T, Kobayashi M, Kawai M, Yoshida R, Sato A, Shishido T, Naito A,
Matsuno K, Okamatsu M, Sakoda Y, Kida H: “Inhibition of avian-origin influenza A(H7N9) virus by the novel capdependent endonuclease inhibitor baloxavir marboxil”, Sci Rep, 9(1):3466 (2019) i) ii)
30) Takehana K, Kinjyo T, Nemoto M, Matsuno K: “Rapid and sensitive detection of elephant endotheliotropic herpesvirus
1 (EEHV1) in blood by loop-mediated isothermal amplification (LAMP)”, J Vet Med Sci, 81 (3), 504-507 (2019) i)
31) Kobayashi A, Qi Z, Shimazaki T, Munesue Y, Miyamoto T, Isoda N, Sawa H, Aoshima K, Kimura T, Mohri S, Kitamoto
T, Yamashita T, Miyoshi I: “Ganglioside synthase knock-out reduces prion disease incubation time in mouse models”,
Am J Pathol,189(3), 677-686 (2019) i) ii)
32) Shibata A, Hiono T, Fukuhara H, Sumiyoshi R, Ohkawara A, Matsuno K, Okamatsu M, Osaka H, Sakoda Y: “Isolationand characterization of avian influenza viruses from raw poultry products illegally imported to Japan by international
flight passengers”, Transbound Emerg Dis, 65 (2), 465-475 (2018) i)
33) Tazaki T, Tabata K, Ainai A, Ohara Y, Kobayashi S, Ninomiya T, Orba Y, Mitomo H, Nakano T, Hasegawa H, Ijiro K,
Sawa H, Suzuki T, Niikura K: “Shape-dependent adjuvanticity of nanoparticle-conjugated RNA adjuvants for
intaranasal inactivated influenza vaccines”, RSC Advances, 8:16527-16536 (2018) i)
34) Hayashida K, Umemiya-Shirafuji R, Sivakumar T, Yamagishi J, Suzuki Y, Sugimoto C, Yokoyama N:” Establishmentof a mouse-tick infection model for Theileria orientalis and analysis of its transcriptome”, Int J Parasitol, 48(12):915924 (2018) i) ii)
35) Noshi T, Kitano M, Taniguchi K, Yamamoto A, Omoto S, Baba K, Hashimoto T, Ishida K, Kushima Y, Hattori K,
Kawai M, Yoshida R, Kobayashi M, Yoshinaga T, Sato A, Okamatsu M, Sakoda Y, Kida H, Shishido T, Naito A: “Invitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus
polymerase PA subunit”, Antiviral Res, 160:109-117 (2018) i)
36) Okamoto M, Fukushima Y, Kouwaki T, Daito T, Kohara M, Kida H, Oshiumi H: “MicroRNA-451a in extracellular,
blood-resident vesicles attenuates macrophage and dendritic cell responses to influenza whole-virus vaccine”, J Biol
Chem, 293(48):18585-18600 (2018) i) ii)
37) Anindita PD, Sasaki M, Okada K, Ito N, Sugiyama M, Saito-Tarashima N, Minakawa N, Shuto S, Otsuguro S, Ichikawa
S, Matsuda A, Maenaka K, Orba Y, Sawa H: “Ribavirin-related compounds exert in vitro inhibitory effects towardrabies virus”, Antiviral Res, 154:1-9 (2018) i)
38) Ohkoshi Y, Sato T, Wada T, Fukushima Y, Murabayashi H, Takakuwa Y, Nishiyama K, Honda H, Shiraishi T, Kuronuma
K, Takahashi H, Nakajima C, Suzuki Y, Yokota SI:“Whole genome analysis of a multidrug-resistant Streptococcus
pneumoniae isolate from a patient with invasive pneumococcal infection developing disseminated intravascular
coagulation”, J Infect Chemother, 24(8):674-681 (2018) i)
39) Yoshida S, Araki T, Asai T, Tsuyuguchi K, Arikawa K, Iwamoto T, Nakajima C, Suzuki Y, Ohya K, Yanai T, Wada T,
Yamamoto T: “Phylogenetic uniqueness of Mycobacterium avium subspecies hominissuis isolated from an abnormal
pulmonary bovine case”, Infect Genet Evol, 62:122-129 (2018) i) ii)
40) Yamasaki T, Suzuki A, Hasebe R, Horiuchi M: “Retrograde Transport by Clathrin-Coated Vesicles is Involved in
Intracellular Transport of PrP Sc in Persistently Prion-Infected Cells”, Sci Rep, 8(1):12241(2018) i)

105

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41) Shibata A, Okamatsu M, Sumiyoshi R, Matsuno K, Wang ZJ, Kida H, Osaka H, Sakoda Y: “Repeated detection of
H7N9 avian influenza viruses in raw poultry meat illegally brought to Japan by international flight passengers”,
Virology, 524:10-17 (2018) i)
42) Sajiki Y, Konnai S, Okagawa T, Nishimori A, Maekawa N, Goto S, Ikebuchi R, Nagata R, Kawaji S, Kagawa Y, Yamada
S, Kato Y, Nakajima C, Suzuki Y, Murata S, Mori Y, Ohashi K: “Prostaglandin E 2 Induction Suppresses the Th1
Immune Responses in Cattle with Johne's Disease”, Infect Immun, 86(5) (2018) i) ii)
43) Liu M, Adjou Moumouni PF, Asada M, Hakimi H, Masatani T, Vudriko P, Lee SH, Kawazu SI, Yamagishi J, Xuan X:“Establishment of a stable transfection system for genetic manipulation of Babesia gibsoni”, Parasit Vectors,
11(1):260 (2018) i)
44) Okagawa T, Konnai S, Nishimori A, Maekawa N, Goto S, Ikebuchi R, Kohara J, Suzuki Y, Yamada S, Kato Y, Murata
S, Ohashi K: “Cooperation of PD-1 and LAG-3 in the exhaustion of CD4 + and CD8 + T cells during bovine leukemia
virus infection”, Vet Res, 49(1),50(2018) i)
45) Honda H, Sato T, Shinagawa M, Fukushima Y, Nakajima C, Suzuki Y, Shiraishi T, Kuronuma K, Takahashi S,
Takahashi H, Yokota SI: “Multiclonal expansion and high prevalence of β-lactamase-negative high-level ampicillinresistant Haemophilus influenzae in Japan, and susceptibility to quinolones”, Antimicrob Agents Chemother, 62(9)(2018) i) ii)
46) Moriyama M, Igarashi M, Koshiba T, Irie T, Takada A, Ichinohe T: “Two conserved amino acids within the NSs of
SFTS phlebovirus are essential for anti-interferon activity”, J Virol, 92(19) (2018) i)
47) Munesue Y, Shimazaki T, Qi Z, Isoda N, Sawa H, Aoshima K, Kimura T, Mohri S, Kitamoto T, Kobayashi A.:“Development of a quick bioassay for the evaluation of transmission properties of acquired prion diseases”, Neurosci
Lett, 668:43-47 (2018), i)48) Nanbo A, Maruyama J, Imai M, Ujie M, Fujioka Y, Nishide S, Takada A, Ohba Y, Kawaoka Y: “Ebola virus requires ahost scramblase for externalization of phosphatidylserine on the surface of viral particles”, PLoS Pathog, 14(1):e1006848 (2018) i)
49) Fujikura D, Muramatsu D, Toyomane K, Chiba S, Daito T, Iwai A, Kouwaki T, Okamoto M, Higashi H, Kida H,
Oshiumi H: “Aureobasidium pullulans-cultured fluid induces IL-18 production, leading to Th1-polarization during
influenza A virus infection”, J Biochem, 163 (1), 31-38 (2018) i)
50) Niikura M, Inoue SI, Fukutomi T, Yamagishi J, Asahi H, Kobayashi F: “Comparative genomics and proteomic analyses
between lethal and nonlethal strains of Plasmodium berghei”, Exp Parasitol, 185, 1-9 (2018)51) Takaki H, Kure S, Oshiumi H, Sakoda Y, Suzuki T, Ainai A, Hasegawa H, Matsumoto M, Seya T: “Toll-like receptor
3 in nasal CD103 + dendritic cells is involved in immunoglobulin A production”, Mucosal Immunol, 11 (1), 82-96(2018) i)
52) Yamasaki T, Suzuki A, Hasebe R, Horiuchi M : “Flow Cytometric Detection of PrPSc in Neurons and Glial Cells from
Prion-Infected Mouse Brains”, J Virol, 92(1). pii: e01457-17 (2017) i)
53) Shan Z, Hirai Y, Hayashi R, Yamasaki T, Hasebe R, Song C-H, Horiuchi M : “Therapeutic effect of autologous compactbone-derived mesenchymal stem cell transplantation on prion disease”. J Gen Virol, 92615-2627 (2017) ii)
54) Nakatsukasa A, Kuruma K, Okamatsu M, Hiono T, Suzuki M, Matsuno K, Kida H, Oyamada T, Sakoda Y:“Potency ofwhole virus particle and split virion vaccines using dissolving microneedle against challenges of H1N1 and H5N1
influenza viruses in mice”, Vaccine, 35(21), 2855-2861(2017) i)

106

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55) Kobayashi M, Kodama M, Noshi T, Yoshida R, Kanazu T, Nomura N, Soda K, Isoda N, Okamatsu M, Sakoda Y,
Yamano Y, Sato A, Kida H : “Therapeutic efficacy of peramivir against H5N1 highly pathogenic avian influenza viruses
harboring the neuraminidase H275Y mutation”, Antiviral Res, 139, 41-48(2017) i) ii)
56) Suzuki M, Okamatsu M, Hiono T, Matsuno K, Sakoda Y: “Potency of an inactivated influenza vaccine prepared from
A/duck/Hokkaido/162/2013 (H2N1) against a challenge with A/swine/Missouri/2124514/2006 (H2N3) in mice”, J Vet
Med Sci, 79 (11), 1815-1821 (2017) i)
57) Fukuhara T, Tamura T, Ono C, Shiokawa M, Mori H, Uemura K, Yamamoto S, Kurihara T, Okamoto T, Suzuki R,
Yoshii K, Kurosu T, Igarashi M, Aoki H, Sakoda Y, Matsuura Y: “Host-derived apolipoproteins play comparable roles
with viral secretory proteins Erns and NS1 in the infectious particle formation of Flaviviridae”, PLoS Pathog, 13(6),e1006475 (2017) i)
58) Isoda N, Asano A, Ichijo M, Wakamori S, Ohno H, Sato K, Okamoto H, Nakao S, Kato H, Saito K, Ito N, Usui A,
Takayama H, Sakoda Y: “Evaluation of control measures for bovine viral diarrhea implemented in Nemuro District,
Hokkaido, Japan, using a scenario tree model”, J Vet Med Sci, 79(7), 1172-1181 (2017) i)
59) Oloniniyi OK, Kurosaki Y, Miyamoto H, Takada A, Yasuda J: “Rapid detection of all known ebolavirus species by
reverse transcription-loop-mediated isothermal amplification (RT-LAMP)”, J Virol Methods, 246, 8-14(2017) i)
60) Takaki H, Oshiumi H, Shingai M, Matsumoto M, Seya T: “Development of mouse models for analysis of human virus
infections”, Microbiol Immunol, 61(3-4), 107-113 (2017) i)
61) Nishimori A, Konnai S, Okagawa T, Maekawa N, Ikebuchi R, Goto S, Sajiki Y, Suzuki Y, Kohara J, Ogasawara S,
Kato Y, Murata S, Ohashi K: “In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1)
rat-bovine chimeric antibody against bovine leukemia virus infection”, PLoS One, 12(4), e0174916 (2017) i)
62) Goto S, Konnai S, Okagawa T, Nishimori A, Maekawa N, Gondaira S, Higuchi H, Koiwa M, Tajima M, Kohara J,
Ogasawara S, Kato Y, Suzuki Y, Murata S, Ohashi K: “Increase of cells expressing PD-1 and PD-L1 and enhancementof IFN-γ production via PD-1/PD-L1 blockade in bovine mycoplasmosis”, Immun Inflamm Dis, 5(3), 355-363 (2017)i)63) Yamaguchi T, Yokoyama K, Nakajima C, Suzuki Y: “Quinolone resistance-associated amino acid substitutions affectenzymatic activity of Mycobacterium leprae DNA gyrase”, Biosci Biotechnol Biochem, 81(7),1343-1347 (2017) i)
64) Maekawa N, Konnai S, Takagi S, Kagawa Y, Okagawa T, Nishimori A, Ikebuchi R, Izumi Y, Deguchi T, Nakajima
C, Kato Y, Yamamoto K, Uemura H, Suzuki Y, Murata S, Ohashi K: “A canine chimeric monoclonal antibody targeting
PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma”, Sci Rep, 7(1), 8951
(2017) i) ii)
65) Okagawa T, Konnai S, Nishimori A, Maekawa N, Ikebuchi R, Goto S, Nakajima C, Kohara J, Ogasawara S, Kato Y,
Suzuki Y, Murata S, Ohashi K: “Anti-Bovine Programmed Death-1 Rat-Bovine Chimeric Antibody for
Immunotherapy of Bovine Leukemia Virus Infection in Cattle”, Front Immunol, 8, 650 (2017) i)
66) Sato T, Ohkoshi Y, Wada T, Fukushima Y, Murabayashi H, Takakuwa Y, Nishiyama K, Shiraishi T, Nakajima
C, Suzuki Y, Yokota SI: “Complete Genome Sequence of Multidrug-Resistant Streptococcus pneumoniae Serotype
19F Isolated from an Invasive Infection in Sapporo, Japan”, Genome Announc, 5(44). pii, e01239-17 (2017) i) ii)
67) Yamagishi J, Asada M, Hakimi H, Tanaka TQ, Sugimoto C, Kawazu SI: “Whole-genome assembly of Babesia ovata
and comparative genomics between closely related pathogens”, BMC Genomics, 18(1), 832 (2017) i) ii)

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68) Kim K, Omori R, Ito K: “Inferring epidemiological dynamics of infectious diseases using Tajima's D statistic on
nucleotide sequences of pathogens”, Epidemics, 21, 21-29 (2017) i)
69) Liu M, Asada M, Cao S, Adjou Moumouni PF, Vudriko P, Efstratiou A, Hakimi H, Masatani T, Sunaga F, Kawazu
SI, Yamagishi J, Xuan X: “Transient transfection of intraerythrocytic Babesia gibsoni using elongation factor-1 alphapromoter”, Mol Biochem Parasitol, 216, 56-59 (2017) i) 4・
70) Takeda Y, Kataoka K, Yamagishi J, Ogawa S, Seya T, Matsumoto M: “A TLR3-Specific Adjuvant Relieves Innate
Resistance to PD-L1 Blockade without Cytokine Toxicity in Tumor Vaccine Immunotherapy”, Cell Rep, 19(9), 18741887 (2017) i) ii)
71) Tarumoto N, Sakai J, Sujino K, Yamaguchi T, Ohta M, Yamagishi J, Runtuwene LR, Murakami T, Suzuki Y, Maeda
T, Maesaki S: “Use of the Oxford Nanopore MinION sequencer for MLST genotyping of vancomycin-resistantenterococci”, J Hosp Infect, 96(3), 296-298 (2017) i)
72) Tsuda Y, Igarashi M, Ito R, Nishio S, Shimizu K, Yoshimatsu K, Arikawa J: “The amino acid at position 624 in theglycoprotein of SFTSV (severe fever with thrombocytopenia virus) plays a critical role in low-pH-dependent cell fusion
activity”, Biomed Res, 38(2), 89-97 (2017) i) ii)
73) Zhao J, Shiratori B, Okumura M, Yanai H, Matsumoto M, Nakajima C, Mizuno K, Ono K, Oda T, Chagan-Yasutan H,
Ashino Y, Matsuba T, Yoshiyama T, Suzuki Y, Hattori T: “Difference in Antibody Responses to Mycobacterium
tuberculosis Antigens in Japanese Tuberculosis Patients Infected with the Beijing/Non-Beijing Genotype”, J Immunol
Res, 2017, 4797856 (2017) i) ii)
74) Nakayama M, Ozaki H, Itoh Y, Soda K, Ishigaki H, Okamatsu M, Sakoda Y, Park CH, Tsuchiya H, Kida H, Ogasawara
K : “Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation incynomolgus macaques after intranasal virus challenge infection”, Pathol Int, 66(12), 678-686 (2016) i) ii)
75) Okamatsu M, Hiono T, Kida H, Sakoda Y : “Recent developments in the diagnosis of avian influenza”, Vet J, 215, 826 (2016) i)
76) Okamatsu M, Motohashi Y, Hiono T, Tamura T, Nagaya K, Matsuno K, Sakoda Y, Kida H: “Is the optimal pH for
membrane fusion in host cells by avian influenza viruses related to host range and pathogenicity?”, Arch Virol, 161(8),2235-42 (2016) i)
77) Shichinohe S, Itoh Y, Nakayama M, Ozaki H, Soda K, Ishigaki H, Okamatsu M, Sakoda Y, Kida H, Ogasawara K:“Comparison of pathogenicities of H7 avian influenza viruses via intranasal and conjunctival inoculation incynomolgus macaques”, Virology, 493, 31-8 (2016) i)
78) Hiono T, Matsuno K, Tuchiya K, Lin Z, Okamatsu M, Sakoda Y: “Complete Genome Sequence of the Avian
Paramyxovirus Serotype 5 Strain APMV-5/budgerigar/Japan/TI/75”, Genome Announc, 4(5), e01005-16 (2016) i) ii)
79) Mitake H, Fujii Y, Nagai M, Ito N, Okadera K, Okada K, Nakagawa K, Kishimoto M, Mizutani T, Okazaki K, Sakoda
Y, Takada A, Sugiyama M: “Isolation of a sp. nov. Ljungan virus from wild birds in Japan”, J Gen Virol, 97(8), 181822 (2016) i)
80) Yamaguchi T, Yokoyama K, Nakajima C, Suzuki Y: “DC-159a Shows Inhibitory Activity against DNA Gyrases ofMycobacterium leprae”, PLoS Negl Trop Dis,10(9), e0005013(2016) i)
81) Matsuba T, Siddiqi UR, Hattori T, Nakajima C, Fujii J, Suzuki Y: “Antigenic characterization of dimorphic surface
protein in Mycobacterium tuberculosis”, FEMS Microbiol Lett, 363(10), fnw082 (2016) i)

108

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82) Seyama T, Hirayasu H, Yoshida G, Ohnuma A, Qiu, Nakajima C, Kasai K, Suzuki Y: “The effects of administering
lactic acid bacteria sealed in a capsule on the intestinal bacterial flora of cattle.” Jpn J Vet Res, 64(3): 197-203 (2016)i)83) Fukui D, Nakamura M, Yamaguchi T, Takenaka M, Murakami M, Yanai T, Fukushi H, Yanagida K, Bando G, Matsuno
K, Nagano M, Tsubota T: “An epizootic of emerging novel avian pox in carrion crows (Corvus corone) and large-billedcrows (Corvus macrorhynchos) in Japan”, J Wildl Dis, 52(2), 230-41(2016) i) ii)
84) Yamagishi J, Sato Y, Shinozaki N, Ye B, Tsuboi A, Nagasaki M, Yamashita R: “Comparison of Boiling and Robotics
Automation Method in DNA Extraction for Metagenomic Sequencing of Human Oral Microbes”, PLoS One, 11(4),e0154389 (2016) i)
85) Matsubayashi M, Kawahara F, Hatta T, Yamagishi J, Miyoshi T, Anisuzzaman, Sasai K, Isobe T, Kita K, Tsuji N:“Transcriptional profiles of virulent and precocious strains of Eimeria tenella at sporozoite stage; novel biologicalinsight into attenuated asexual development”, Infect Genet Evol, pii, S1567-1348 (16) 30052-1 (2016) i)
86) Hiono T, Okamatsu M, Yamamoto N, Ogasawara K, Endo M, Kuribayashi S, Shichinohe S, Motohashi Y, Chu DH,
Suzuki M, Ichikawa T, Nishi T, Abe Y, Matsuno K, Tanaka K, Tanigawa T, Kida H, Sakoda Y : “Experimental infectionof highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats
for the evaluation of their roles in virus transmission”, Vet Microbiol, 182, 108-15 (2016) i)
87) Oshiumi H, Mifsud EJ, Daito T: “Links between recognition and degradation of cytoplasmic viral RNA in innate
immune response”, Rev Med Virol, 26(2), 90-101(2016) i) ii)
88) Hakimi H, Yamagishi J, Kegawa Y, Kaneko O, Kawazu S, Asada M: “Establishment of transient and stable transfection
systems for Babesia ovata”, Parasit Vectors, 9, 171 (2016) i)
89) Gamoh K, Nakamizo M, Okamatsu M, Sakoda Y, Kida H, Suzuki S: “ Protective efficacy of stockpiled vaccine against
H5N8 highly pathogenic avian influenza virus isolated from a chicken in Kumamoto prefecture, Japan, in 2014”, J Vet
Med Sci, 1;78(1), 139-42 (2016) i)
90) Kobayashi S, Suzuki T, Kawaguchi A, Phongphaew W, Yoshii K, Iwano T, Harada A, Kariwa H, Orba Y, Sawa H:“Rab8b regulates transport of West Nile virus particles from recycling endosomes.”, J Biol Chem, 291(12), 6559-68(2016) i)
91) Abe Y, Tamura T, Torii S, Wakamori S, Nagai M, Mitsuhashi K, Mine J, Fujimoto Y, Nagashima N, Yoshino F, Sugita
Y, Nomura T, Okamatsu M, Kida H, Sakoda Y: “Genetic and antigenic characterization of bovine viral diarrhea viruses
isolated from cattle in Hokkaido, Japan”, J Vet Med Sci, 78(1), 61–70 (2016) i) ii)
92) Itoh Y, Shichinohe S, Nakayama M, Igarashi M, Ishii A, Ishigaki H, Ishida H, Kitagawa N, Sasamura T, Shiohara M,
Doi M, Tsuchiya H, Nakamura S, Okamatsu M, Sakoda Y, Kida H, Ogasawara K: “Emergence of H7N9 influenza A
virus resistant to neuraminidase inhibitors in nonhuman primates”, Antimicrob Agents Chemother, 59(8),4962-73(2015) i) ii)
93) Kozasa T, Abe Y, Mitsuhashi K, Tamura T, Aoki H, Ishimaru M, Nakamura S, Okamatsu M, Kida H, Sakoda Y :“Analysis of a pair of END+ and END- viruses derived from the same bovine viral diarrhea virus stock reveals theamino acid determinants in Npro responsible for inhibition of type I interferon production”, J Vet Med Sci, 77(5), 5118 (2015) i)

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94) Kawahara R, Seto K, Taguchi M, Nakajima C, Kumeda Y, Suzuki Y: “Characterization of third-generationcephalosporin-resistant shiga toxin-producing strains of Escherichia coli O157:H7 in Japan”, J Clin Microbiol, 53(9),3035-8 (2015) i) ii)
95) Usami O, Nakajima C, Endo S, Inomata S, Kanamori H, Hirakata Y, Uchiyama B, Kaku M, Suzuki Y, Hattori T: “Acase of Manila type Mycobacterium tuberculosis infection in Japan”, Clin Case Rep, 3(7), 622-5 (2015) i) ii)
96) Ozawa M, Matsuu A, Yonezawa K, Igarashi M, Okuya K, Kawabata T, Ito K, Tsukiyama-Kohara K, Taneno A, Deguchi
E: “Efficient isolation of swine influenza viruses by age-targeted specimen collection”, J Clin Microbiol, 53(4):13318 (2015) i)
97) Sato Y, Yamagishi J, Yamashita R, Shinozaki N, Ye B, Yamada T, Yamamoto M, Nagasaki M, Tsuboi A: “Interindividual differences in the oral bacteriome are greater than intra-day fluctuations in individuals”, PLoS One, 10(6),e0131607 (2015) i)
98) Sakurai A, Takayama K, Nomura N, Kajiwara N, Okamatsu M, Yamamoto N, Tamura T, Yamada J, Hashimoto
M, Sakoda Y, Suda Y, Kobayashi Y,Kida H, Shibasaki F: “Fluorescent immunochromatography for rapid and sensitivetyping of seasonal influenza viruses”, PLoS One, 10(2), e0116715 (2015) i)
99) Tamura T, Mine J, Torii S, Fujimoto Y, Okamatsu M, Sakoda Y : “Pathogenicity of border disease virus FNK2012-1
strain isolated from a pig in the natural host, sheep”, J Vet Med Sci, 77(3), 341-3 (2015) i)
100)

Kobayashi S, Orba Y, Yamaguchi H, Takahashi K, Sasaki M, Hasebe R, Kimura T, Sawa H: “Autophagy inhibits

viral genome replication and gene expression stages in West Nile virus infection”, Virus Res, 191, 83-91 (2014) i) ii)
3

Published books
Number of books: #5

1) Carr MJ, Gonzalez G, Teeling EC, Sawa H: “Bat Polyomaviruses: A Challenge to the Strict Host-Restriction Paradigm
within the Mammalian Polyomaviridae.” In Bats and Viruses: Current Research and Future Trends, Corrales-Aguilar
E, Schwemmle M (ed), Caister Academic Press, U.K.:87-118 (2020), ISBN: 978-1-912530-14-4 i)
2) Yamaguchi T, Nakajima C, Suzuki Y: “Acquisition of drug resistance by Mycobacterium tuberculosis –Tuberculosis
and nontuberculous mycobacteriosis. The expert’s lecture on recent findings useful for actual clinical activiries”,
Respiratory Journal,64(4): 650-656 (2018) i)
3) Villanueva MA, Mingala CN, Nakajima C, Suzuki Y: “Emerging Infectious Diseases in Water Buffalo – An economic
and Public Health Concern.” Intech Open Access Publisher, Rijeka, Croatia, doi: 10.5772/intechopen.73136 (2018) i)
4) Kongsoi S, Nakajima C, Suzuki Y: “Quinolone Resistance in Non-typhoidal Salmonella.” In Current Topics in
Salmonella and Salmonellosis, Mares M (eds.), Intech Open Access Publisher, Rijeka, Croatia:115-135 (2017) i)
5) Thapa J, Nakajima C, Gairhe KP, Maharjan B, Paudel S, Shah Y, Mikota SK, Kaufman GE, McCauley D, Tsubota T,
Gordon SV, Suzuki Y: “Wildlife tuberculosis: An emerging threat for conservation in South Asia.” In Global Expositionof Wildlife Management. Cardona P-J (eds.), Intech Open Access Publisher, Rijeka, Croatia: 73-90 (2017) i)

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4

Oral presentations
4.1

1)

Keynote lectures/Invited lectures: #76

Ayato Takada: “Approaches for the development of therapeutics for Ebola virus disease”, University of Miyazaki,
Miyazaki, Japan, Open seminar for infectious diseases, 2020.1.24 [Domestic conference] (invited speaker)

2)

Yoshihiro Sakoda: “Classical swine fever outbreaks in Japan in 2018-2019 and related research activities”, Tamsui,
Taiwan, Experience Exchange on Prevention Techniques and Training Course of Diagnosis of Classical Swine Fever,2019.11.19 [International symposium] (invited speaker)

3)

Yoshihiro Sakoda: “Classical swine fever outbreaks in Japan in 2018-2019”, China Institute of Veterinary Drug
Control, Beijing, China, International Symposium for Classical Swine Fever, 2019.10.23-26 [International
symposium] (invited speaker)

4)

Yoshihiro Sakoda: “Classical swine fever outbreaks in Japan in 2018-2019”, Animal and Plant Quarantine Agency,
Korea, Seminar for Classical Swine Fever, 2019.10.15 [International symposium] (invited speaker)

5) Hirofumi Sawa, William Hall: “Tactics for Global Infectious Diseases Control”, Tsukuba International Congress
CenterTsukuba Conference, Ibaraki, Japan, Tsukuba Conference 2019, 2019.10.3 [International conference] (invited
speaker)6)

Stephen Gordon: “One Health route to exploring virulence in the Mycobacterium tuberculosis complex”, The GrandHall & Winter Gardens at The Drum at Wembley, London, UK, VALIDATE-BSI 2019 Conference, 2019.10.3[International conference] (Invited Speaker)

7)

Chie Nakajima, Yasuhiko Suzuki: “Genetic analyses of multidrug-resistant Mycobacterium tuberculosis clinicalisolates collected in Asian countries.”, Awaji Yumebutai International Conference Center, Awaji, Japan, The 18th Awaji
International Forum on Infection and Immunity, 2019.9.11 [International symposium] (invited speaker)

8) Ayato Takada: “Recent topics on Filovirus research”, Tsukuba international congress center, Tsukuba, Japan, The 162nd
Meeting of the Japanese Society of Veterinary Science, Symposium “Infectious diseases threatening humans andanimals”, 2019.9.10 [Domestic conference] (invited speaker)
9)

Chie Nakajima: “Development of a Simple and Rapid Drug-resistant Campylobacter Detection Method Utilizing
DNA-array Technique”, University of San Agustin, Ilo Ilo city, the Philippines, The 4th International Symposium on
Livestock Biotechnology, 2019.7.15 [International symposium] (invited speaker)10) William Hall: “Special lecture: Infectious diseases caused by flaviviruses,” Enyu Gakusya, Hokkaido University,
Sapporo, Japan, Symposium and Workshop for Diagnosis-by-Sequencing using MinION, 2019.7.10 [International
symposium] (invited speaker)11) Ayato Takada: “Ebola and Marburg hemorrhagic fever”, Sapporo Convention Center, Sapporo Japan, The 8th Annual
Meeting of the Japan Psychiatric Medical Conference, 2019.7.5 [Domestic conference] (invited speaker)
12) Yoshihiro Sakoda: “How to implement cooperation among Asian countries for the control of highly pathogenic avian
influenza (HPAI)?”, National Institute for Environmental Studies, Japan, NIES_NIER_USGS International workshop
2019, 2019.5.21-23 [International symposium] (invited speaker)
13) Stephen Gordon: “Exploring the molecular basis of virulence in the Mycobacterium tuberculosis complex”, Sapporo
Convention Center, Sapporo, Japan, The 92nd Annual Meeting of Japanese Society for Bacteriology, 2019.4.23[International symposium] (Invited Speaker) *111

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14) Chie Nakajima, Yasuhiko Suzuki, Jeewan Thapa: “Development of new methods for the characterization of bacterial
pathogens”, Sapporo Convention Center, Sapporo, Japan, The 92nd Annual Meeting of Japanese Society for
Bacteriology, 2019.4.23 [International symposium] (invited speaker) *15) Chie Nakajima: “Genetic analyses of multidrug-resistant Mycobacterium tuberculosis”, National University ofSingapore, Singapore, Asia - Pacific Scientific Workshop 2019.3.5 [International symposium] (invited speaker)16) Yasuhiko Suzuki, Chie Nakajima: “Molecular epidemiology of human and animal tuberculosis in Asian countries”, La
Thanh Hotel, Hanoi, Vietnam, 21st International Conference on Emerging Infectious Diseases in the Pacific Rim,
2019.2.26 [International symposium] (invited speaker) *17) Norikazu Isoda: “Antimicrobial resistance survey in Thailand”, Thammasat University, Rangsit, Thailand, 3rd One
Health lecture Series on Antimicrobial Resistance, Faculty of Public Health, 2018.12.20 [International symposium](invited speaker)18) Takada Ayato: “Toward the control of viral zoonoses: Our SATREPS activity in Africa”, Nagasaki University, Nagasaki,
Japan, The 59th Annual Meeting for the Japanese Society of Tropical Medicine, 2018.11.10 [Domestic conference](invited speaker)19) Stephen Gordon: “Zoonotic Tuberculosis: Comparative analyses of the human and bovine tubercle bacilli” , The
Hague, Netherlands, The 49th Union World Conference on Lung Health, 2018.10.26 [International conference](Invited speaker)20) Yasuhiko Suzuki: “Zoonosis Control”, University of the Philippines Cebu, Cebu, The Philippines, 3rd International
Livestock Biotechnology Symposium, 2018.7.16 [International symposium] (invited speaker) *21) Ayato Takada: “Recent advances in Ebola virus research”, Nitori Cultural Hall, Sapporo, Japan, The 20th Annual
Meeting of the Japan Society for Health Care Management, 2018.6.8 [Domestic conference] (invited speaker)22) Chie Nakajima: “The current situation of multidrug-resistant tuberculosis in Asia and development of rapid genetic
diagnostic methods”, Nippon Veterinary and Life Science University, Tokyo, Japan, The 45th Symposium of theJapanese Society of Antimicrobials for Animals, 2018.4.28 [Domestic symposium] (invited speaker)23) Ayato Takada: “Recent Topics from Ebola virus Research”, Inner Mongolia Agriculture University, Hohhot, Inner
Mongolia, Inner Mongolia Agriculture University Seminar, 2018.4.18 [International conference] (invited speaker)24) Ayato Takada: “Filoviruses”, Fukuoka Convention Center, Fukuoka, The 91th Annual Meeting of Japanese Society for
Bacteriology, 2018.3.27 [Domestic conference] (invited speaker)25) Hirofumi Sawa: “Development of anti-viral compounds for zoonotic viral diseases”, Mahidol University, Bangkok,
Thailand, International Joint Forum on Infectious Disease Research 2018, 2018.2.28 [International symposium](invited speaker)26) Hiroshi Kida: “For the cotrol of avian influenza and the preparedness for pandemic influenza”, Rangsit Campus,
Thammasat University, Thailand, A special Lecture, 2017.12.4 (invited lecture)27) Ayato Takada: “Recent advances in Ebola virus Research”, Keio Plaza Hotel, Tokyo, The 66th Annual Regional Meetingof the Japanese Association for Infectious Diseases, 2017.11.1 [Domestic conference]28) Hirofumi Sawa, Keita Matsuno, Ryo Nakao, Michihito Sasaki, Yasuko Orba: “Discovery of diverse arthropod
bunyaviruses in field-collected mosquitoes and ticks and their evolution”, Osaka International Convention Center,
Osaka, Japan, The 65th Annual Meeting of the Japanese Society for Virology. 2017.10.26 [International symposium](invited speaker)

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,29) Yoshihiro Sakoda: “Current situation of H5Nx highly pathogenic avian influenza epidemic in the world”, Beijing,
China, China & Asia-Pacific Conference on Emerging Infectious Diseases (CAPEID), 2017.9.12-15 [International
conference]30) Keita Matsuno, Masahiro Kajihara, Nodoka Kasajima, Ryo Nakao, Shiho Torii, Hiroshi Shimoda, Ken Maeda, Ayato
Takada, Hideki Ebihara, Hirofumi Sawa: “Genetic diversity among phleboviruses identified in ticks; implication of
distinct evolutional pathways of phleboviruses”, Awaji Yumebutai International Conference Center, Hyogo, Japan,
The 16th Awaji International Forum on Infection and Immunity. 2017. 9.8 [International conference] (invited speaker)
31) Keita Matsuno: “Genetic diversity among phleboviruses identified in ticks; implication of distinct evolutional pathwaysof phleboviruses”, Awaji, Hyougo, The 16th Awaji International Forum on Infection and Immunity, 2017.9.5-8[International conference]32) Ayato Takada: “Genetic Predisposition to Acquire a Polybasic Cleavage Site for Highly Pathogenic Avian Influenza
Virus Hemagglutinin”, B-nest Pegasart, Shizuoka, The 31st Annual Symposium for Japanese Influenza Virologist,2017.6.9 [Domestic symposium]33) Axel Martinelli: “Detection of loci under selection using Linkage Group Selection (LGS) in vitro” Hokkaido University,
Sapporo, The 86th Annual Meeting of the Japanese Society of Parasitology, 2017.5.29 [Domestic conference]34) Ayato Takada: “Ebolavirus --Ecology and antiviral strategies--”, Korea University, Seoul, 11th Annual Meeting of
Korean Society of Zoonosis, 2017.5.19 [International conference]35) Ayato Takada: “Recent advances in Ebola virus Research”, Kobe Convention Center, Kobe, The 32nd Annual Meetingof Japanese Society for Infection Prevention and Control, 2017.2.25 [Domestic conference]36) Yoshihiro Sakoda: “Challenges for providing technical training HPAI and LPAI: Research Center for Zoonosis
Control, Hokkaido University (Japan)”, Tokyo, Japan, Regional Meeting of OIE Reference Centers in Asia and thePacific, 2017.2.6-7 [International Conference]37) Hiroshi Kida: “How to control avian influenza and how to prepare for future pandemics in humans”, Rangsit Campus,
Thammasat University, Thailand, Keynote Lecture for Lecture Series on One Health First Meeting on TechnicalCooperative Network, 2016.11.15 (invited lecture)38) Michael Carr: "Identification of the same polyomavirus species in different African horseshoe bat species is indicativeof short-range host-switching", Osaka International Convention Center, Osaka, The 65th Annual Meeting of theJapanese Society for Virology, 2016.10.26 [Domestic conference]39) Hiroshi Kida: “We are prepared for pandemic influenza”,Sapporo Convention Center, Sapporo, Japan, The 8thInternational Global Virus Network Meenting, 2016. 10.25 [International conference]40) Ayato Takada: “Neutralization and Antibody-Dependent Enhancement of Ebolavirus”, Sapporo Convention Center,
Sapporo, 8th International Global Virus Network Meeting, 2016.10.25 [International conference]41) Ayato Takada: “Biochemistry for sustainable global health, Recent advances in diagnostics and therapeutics for Ebola
virus disease”, Sendai International Center, Sendai, The 89th Annual Meeting of the Japanese Biochemical Society,2016.9.25 [Domestic conference]42) Ayato Takada: “Ebolavirus Entry into Cells –Neutralization and Antibody-Dependent Enhancement–”, Awaji
Yumebutai International Conference Center, Awaji, The 15th Awaji International Forum on Infection and Immunity,
2016.9.9 [International conference]

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43) Hiroshi Kida: “Control of avian influenza and preparedness for pandemic influenza”. Asia-Pacific WHO/OIE/FAO
Joint Workshop on Surveillance Prevention and Control of Zoonotic influenza, Paro, Bhutan, 2016.8.30 [International
conference] (invited speaker)44) Ayato Takada: “Influenza as a Zoonosis”, Izumi Garden, Tokyo, The 24th Meeting of Respiratory/Infectious Disease
Study Group, 2016.8.20 [Domestic conference]45) Brendon Yew Loong Chua:"Multi-tasking an influenza vaccine to provide rapid and long-term protection against
influenza and secondary pneumococcal infection”, Albufeira, Portugal, Engineering Conference International on
Vaccine Technology VI, 2016.7.16[International conference]46) Hiroshi Kida: “We are prepared for pandemic influenza”, WHO Collaborating Centere Conference Room, Hokkaido
University, Sapporo, Japan, The 4th Meeting of the Consortium for the Control Zoonoses, 2016.7.8 [Domestic
conference]47) Hiroshi Kida: “Pandemic influenza as an example of emerging zoonoses” University of Zambia School of Veterinary
Medicine Veterinary School Main Lecture Theatre. Lusaka, Zambia, 2016.6.14 [International Conference] (invitedlecture)48) Hiroshi Kida: “Pandemic influenza as an example of emerging zoonoses”, Nagasaki University, Nagasaki, Japan, 2016
Training Course for Tropical Medicine,2016.6.3 (invited lecture)49) Ayato Takada: “Recent Topics on Zoonosis Research –Ebola hemorrhagic fever–”, Fukuoka Convention Center,
Fukuoka, The 63rd Annual Meeting of the Japanese Society of Anesthesiologist, 2016.5.26 [Domestic conference]50) Hiroshi Kida: “Looking back and forward on One Health Strategy - 40 years struggle for the control of zoonoses”,
School of Veterinary Medicine, Hokkaido University, Sapporo, Japan, Special Lecture, 2016.5.2 (invited lecture)51) Ayato Takada: “Recent Topics on Ebola Virus Research”, Sendai International Center, Sendai, The 90th Annual Meetingof the Japanese Association for Infectious Diseases, 2016.4.16 [Domestic conference]52) Ayato Takada: “Recent Topics on Zoonosis Research –Ebola hemorrhagic fever and Influenza–”, Nagoya University,
Nagoya, 45th Noyori Forum, 2016.4.15 [Domestic conference]53) Arnab Pain: “Chromerid genomes reveal the evolutionary path and genomic adaptations from photosynthetic algae to
obligate intracellular parasitism”, International House, Osaka, The 89th annual meeting of Japanese Society for
Bacteriology, 2016.3.24 [Domestic conference]54) Ayato Takada: “Ecology of Viruses”, Kokuyo Hall, Tokyo, Kickoff Symposium for the Inter-University ResearchInstitute Corporation, National Institutes for the Humanities, 2016.3.19 [Domestic symposium]55) Kimihito Ito: “On the analysis of genetic sequence data of influenza viruses”, JST Tokyo, Big Data Application
International Symposium, 2016.3.4 [International symposium]56) Axel Martinelli: “A multidisciplinary approach to uncover the genetic basis of selectable phenotypes”, JST Tokyo, Big
Data Application International Symposium, 2016.3.4 [International symposium]57) Ayato Takada: “A monoclonal antibody neutralizing all known ebola viruses”, National Institute of Allergy And
Infectious Diseases (NIAID) National Institutes Of Health (NIH), Rockville, 2016 US–Japan Annual Medical
Biodefense Research Symposium Theme: “Ebola And Emerging Pathogens”, 2016.1.14 [International symposium]58) Hiroshi Kida: “Points for the control of avian influenza and preparedness for future pandemics.”, The Bethesda North
Marriott Hotel and Conference Center, Bethethda, United States of America, The 18th Respiratory Infections (ARI)
Panel Meeting, 2016.1.14 [International conference]

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59) Yoshihiro Sakoda, “Characterization of avian influenza viruses recently isolated in Japan”, Tamsui, Taiwan
2015 International Conference on Prevention and Control of Avian Influenza, 2015.10.21 [International conference]60) Ayato Takada: “Ebolavirus: ecology and antiviral strategies”, Davos Congress Centre, Davos, 3rd GRF One HealthSummit 2015, 2015.10.5 [International conference]61) Stephen Gordon: “Tuberculosis and One Health: defining host preference across the Mycobacterium tuberculosis
complex,” Lecture Hall, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan, The 3rd Sapporo
Summer Symposium for One Health 2015, 2015.9.16-17 [International symposium] (invited speaker)62) Yoshihiro Sakoda: “Contributions on the zoonosis control from veterinary medicine”, Aomori, Japan, Aomori Branchof the Japan Veterinary Medical Association, 2015.9.12 [Domestic conference]63) David Charles Jackson: “How to elicit immediate and long-term immunity against influenza”, Crown Plaza London,
International Conference on Influenza, 2015.8.25 [International conference]64) Hiroshi Kida: “For the control of avian and human influenza”, Crown Plaza London, International Conference on
Influenza, 2015.8.24 [International conference]65) Lorena E. Brown: “Inducing cross-reactive responses”, Crown Plaza London, International Conference on Influenza,2015.8.24 [International conference]66) Ayato Takada: “Ebola hemorrhagic fever”, Kyoto Terrasa Hall, Kyoto, The 62th annual meeting of Japanese
Association for Laboratory Animal Science, 2015.5.28 [Domestic conference]67) Yoshihiro Sakoda: “Research activities in Hokkaido University for the control of avian influenza”, Korea, International
Workshop on Highly Pathogenic Avian Influenza and Bird Migration, 2015.5.27 [International conference]68) Yasuhiko Suzuki: “Tuberculosis - clear and present danger at natural disasters”. Sendai City Hall, Sendai, Japan, The
3rd World Conference on Disaster Risk Reduction. 2015.3.18 [International conference]69) Yoshihiro Sakoda: “Diagnosis and identification of highly pathogenic avian influenza viruses recently isolated in Asia”,
Tamsui, Taiwan, 2015 International Conference on Prevention and Control of Avian Influenza, 2015.3.11 [International
conference]70) Ayato Takada: “Comparison of antiviral activity between IgA and IgG specific to influenza virus hemagglutinin:
Increased potential of IgA for heterosubtypic immunity”, Academia Sinica, Taipei, "Improving efficacy of vaccines for
ARI", Acute Respiratory Infections (ARI) Panel Meeting, 17th International Conference on Emerging Infectious
Diseases (EID) in the Pacific Rim Emerging Viral Diseases, United States–Japan Cooperative Medical Sciences
Program, 2015.1.28 [International conference]71) Yasuhiko Suzuki: “Collaboration on tuberculosis control in Zambia”, Protea Hotel Stellenbosh, Stellenbosh, South
Africa, Global Research Council Africa Summit, 2014.11.24 [International conference]72) Yoshihiro Sakoda: “Characterization of highly pathogenic avian influenza virus recently isolated in Japan”, Tamsui,
Taiwan, 2014 International Conference on Prevention and Control of Avian Influenza, 2014.11.18 [International
conference]73) Brendon Yew Loong Chua: “Harnessing innate and adaptive immunity against influenza and bacterial co-infections”,
Melbourne, Australia, Australian Influenza Symposium, 2014.11.12 [International symposium]74) William Hall: “One Health: Importance of virus infections and a focus on Vietnam,” Lecture Hall, Faculty of Veterinary
Medicine, Hokkaido University, Sapporo, Japan, The 2nd Sapporo Summer Seminar for One Health (SaSSOH) 2014,2014.9.24-25 [International conference] (keynote speaker)

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75) Hiroshi Kida: “Control of avian influenza and preparedness for pandemic influenza”, Tokyo University, Tokyo, OIE
Regional Workshop on Enhancing Influenza A virus National Surveillance Systems OIE/JTF Project for Controlling
Zoonoses in Asia under One Health Concept, 2014.8.26 [International conference]76) Ayato Takada: “Role of antibodies in protective immunity against filovirus infection”, Hotel Galvez, Galveston, 6thInternational Symposium on Filoviruses, 2014.4.2 [International symposium]
4.2

Other presentations:#18

1) Kosuke Okuya, Reiko Yoshida, Rashid Manzoor, Shinji Saito, Tadaki Suzuki, Osamu Ichii, Hideaki Higashi, Ayato
Takada: “A potential role of non-neutralizing IgA antibody for cross-protective immunity against influenza A viruses”,
Tower-Hall Funabori, Tokyo, The 67th Annual Meeting of the Japanese Society for Virology, 2019.10.31 [Domestic
conference]2) Keita Mizuma, Keita Matsuno, Masatoshi Okamatsu, Ayato Takada, Yoshihiro Sakoda: “A functional analysis of hostRNAs binding with the nucleoprotein of severe fever with thrombocytopenia syndrome virus”, Tower-Hall Funabori,Tokyo, The 67th Annual Meeting of the Japanese Society for Virology, 2019.10.30 [Domestic conference]3) Mao Isono, Wakako Furuyama, Makoto Kuroda, Tatsunari Kondoh, Manabu Igarashi, Masahiro Kajihara, Reiko
Yoshida, Rashid Manzoor, Kosuke Okuya, Hiroko Miyamoto, Heinz Feldmann, Andrea Marzi, Masahiro Sakaitani,
Ayato Takada: “Searching chemical compounds for development of the entry inhibitor against ebolavirus”, TowerHall Funabori, Tokyo, The 67th Annual Meeting of the Japanese Society for Virology, 2019.10.30 [Domestic
conference]4) Masahiro Kajihara, Katendi Changula, Bernard Hang’ombe, Hayato Harima, Hiroko Miyamoto, Yoshiki Eto, Kosuke
Okuya, Mao Isono, Reiko Yoshida, Yongjin Qiu, Akina Mori-Kajihara, Yasuko Orba, Hirofumi Sawa, Hirohito Ogawa,David Squarre, Victor Mukonka, Aaron Mweene, and Ayato Takada: “Genetic analyses of marburgvirus in Egyptian
fruit bats in Zambia”, Tower-Hall Funabori, Tokyo, The 67th Annual Meeting of the Japanese Society for Virology,
2019.10.30 [Domestic conference]5) Keita Mizuma, Keita Matsuno, Masatoshi Okamatsu, Ayato Takada, Yoshihiro Sakoda: “Profiling RNAs binding with
the nucleoprotein of severe fever with thrombocytopenia syndrome virus (SFTSV) revealed orchestrated replication ofa segmented RNA virus”, Glasgow, United Kingdom, International meeting on arboviruses and their vectors (IMAV2019), 2019.9.5-6[International conference]
6) Augustin Twabela, George Tshilenge, Thanh-Lam Nguyen, Keita Matsuno, Isabella Monne, Bianca Zecchin,
Masatoshi Okamatsu, Yoshihiro Sakoda: “Characterization of H5N8 highly pathogenic Avian Influenza Virus isolated
in democratic republic of Congo in 2017”, SUNTEC, Singapore, Options X for the Control of Influenza, 2019.8.289.1[International conference]7) Yuto Kikutani, Masatoshi Okamatsu, Shoko Nishihara, Sayaka Takase-Yoden, Takahiro Hiono, Ryan Mcbride, Robert
P. De Vries, Keita Matsuno, Hiroshi Kida, Yoshihiro Sakoda: “H6 chicken influenza virus recognizes sulfated α2,3Sialylated glycans as the receptors”, SUNTEC, Singapore, Options X for the Control of Influenza, 2019.8.289.1[International conference]

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,8) Brendon Chua: “Development of TLR2-against-based immunostimulants against respiratory pathogens,” Lecture Hall,
Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan, Wise Program for One Health Frontier
Graduate School of Excellence, 2019.2.27 [Special lecture]9) Keita Matsuno, Masahiro Kajihara, Syun-ichi Urayama, Ryo Nakao, Miho Hirai, Yongjin Qiu, Takuro Nunoura, Aaron
S Mweene, Bernard M Hang’ombe, Martin Simuunza, Masatoshi Okamatsu, Yoshihiro Sakoda, Hirofumi Sawa, Ayato
Takada:“Discoveries of novel viruses in ticks and fruit bats by using FLDS method and MinION sequencer”, Osaka
International Convention Center, Osaka, Japan, The 65th Annual Meeting of the Japanese Society for Virology,
2017.10.24-26 [International conference]*
10) Lam Thanh Nguyen, Kazunari Nakaishi, Keiko Motojima, Ayako Ohkawara, Takahiro Hiono, Keita Matsuno,
Masatoshi Okamatsu, Ayato Takada, Hiroshi Kida, Yoshihiro Sakoda: “Rapid and broad detection of H5 hemagglutinin
by an immunochromatographic kit using novel monoclonal antibody against a clade 2.3.4.4 highly pathogenic avian
influenza virus”, Osaka International Convention Center, Osaka, Japan, The 65th Annual Meeting of the JapaneseSociety for Virology, 2017.10.24-26 [International conference]*11) Nodoka Kasajima, Keita Matsuno, Shiho Torii, Takahiro Hiono, Masatoshi Okamatsu, Hideki Ebihara, Yoshihiro
Sakoda: “Suppression of PKR signaling pathway by nonstructural protein of severe fever with thrombocytopenia
syndrome virus”, Osaka International Convention Center, Osaka, Japan, The 65th Annual Meeting of the JapaneseSociety for Virology, 2017.10.24-26 [International conference] *12) Masatoshi Okamatsu, Takahiro Hiono, Keita Matsuno, Lam Thanh Nguyen, Mizuho Suzuki, Yuto Kikutani, Hiroshi
Kida,Yoshihiro Sakoda: “Characterization of H5N6 highly pathogenic avian influenza viruses isolated from wild andcaptive birds in the winter of 2016–2017 in northern Japan”, Osaka International Convention Center, Osaka, Japan,
The 65th Annual Meeting of the Japanese Society for Virology, 2017.10.24-26 [International conference]*13) Hirofumi Sawa, Shintaro Kobayashi, Hiroki Yamaguchi, Wallaya Phongphaew, Michihito Sasaki, Yasuko Orba:“Examination of neuronal injury by West Nile virus infection”, Royton Sapporo, Sapporo, Japan, The 59th Annual
Meeting of the Japanese Society of Neurology”, 2017.5.23-26 [International conference] *14) Arnab Pain: “Chromerid genomes reveal the evolutionary path and genomic adaptations from photosynthetic algae to
obligate intracellular parasitism,” International House Osaka, Osaka, Japan, The 89th Annual Meeting of JapaneseSociety for Bacteriology, 2016.3.24 [International conference]
15) Shintaro Kobayashi, Wallaya Phongphaew, Kentaro Yoshii, Minato Hirano, Memi Muto, Yasuko Orba, Hirofumi
Sawa, Hiroaki Kariwa: “Analysis of the accumulation mechanism of denatured proteins by West Nile virus infection,”
Fukuoka International Congress Center, Fukuoka, Japan, The 63rd Annual Meeting of the Japanese Society for
Virology, 2015.11.22-24 [International conference]16) Yoshihiro Sakoda: “Host or virus derived secretory membrane binding proteins are involved in formation of infectious
Flavivirus particles,” Fukuoka International Congress Center, Fukuoka, Japan, The 63rd Annual Meeting of theJapanese Society for Virology, 2015.11.22-24 [International conference]17) Hirofumi Sawa: “Epidemiological and Basic Research Activities Targeting Polyomaviruses,” Awaji Yumebutai
International Conference Center, Japan, The 14th Awaji International Forum on Infection and Immunity, 2015.9.8[International conference]

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18) Junya Yamagishi: “How to approach the diversity in transcriptiome, a key to elucidate host-parasite interaction in
genomic era,” Awaji Yumebutai International Conference Center, Japan, The 14th Awaji International Forum on
Infection and Immunity, 2015.9.11 [International conference]
5

Patent applications
Number of patent applications: # 32 (Japanese patents: # 12, overseas patents: # 20)
Number of patent registrations (of the above number): # 26
5.1

Registration information

1) Expression vector for producing protein derived from foreign gene in large quantity using animal cells, and use thereof,
National University Corporation Hokkaido University, Fuso Pharmaceutical Industries Ltd, Canada Patent 2748011,
2018 11. 23. Tahara H, Suzuki Y, Yamamoto K, Kitahara Y, Suzuki Y.
2) Microneedle array containing inactivated whole-virus-particle vaccine and the administration method, FUJIFILM
Corporation, National University Corporation Hokkaido University
Japan Patent 2018-39839, 2018.3.15, Koji Kuruma, Takayoshi Oyamada, Toshio Shimada, Yoshihiro Sakoda,
Hiroshi Kida
3) Recombinant vaccinia virus coding hemagglutinin gene derived from a novel influenza virus, Tokyo Metropolitan
Institute of Medical Science, The Chemo-Sero-Therapeutic Research Institute (Kaketsuken), National University
Corporation Hokkaido University
Japan Patent 2016-178945, 2016.10.13, Michinori Kohara, Fumihiko Yasui, Toshio Murakami, Hiroshi Kida, Yoshihiro
Sakoda4) Protein substance having triple helix structure and manufacturing method therefor cell and use thereof,
National University Corporation Hokkaido University, Fuso Pharmaceutical Industries, Ltd
Canada Patent 2748015, 2017.02.28, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
Korea patent 10-1686688, 2016.12.08, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
Hong Kong Patent HK1163153, 2015.09.18, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
EU Patent 2380979, 2015.04.15, Suzuki Y, Tahara H, Yamamoto K, Kitahara Y, Suzuki Y
Japan Patent 5645187, 2014.10.20, Suzuki Y, Tahara H, Yamamoto K, Kitahara Y, Suzuki Y
Australia Patent 2009331327, 2014.04.01, Suzuki Y, Tahara H, Yamamoto K, Kitahara Y, Suzuki Y5) Expression vector for Mass production of foreign gene-derived protein using animal cell and use thereof,
National University Corporation Hokkaido University, Fuso Pharmaceutical Industries, Ltd.
EU patent 2258843, 2016.11.11, Tahara H, Suzuki Y, Yamamoto K, Kitahara Y, Suzuki Y
Japan Patent 6022518, 2016.10.14, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
Korea patent 10-1655492, 2016.09.01, Tahara H, Suzuki Y, Yamamoto K, Kitahara Y, Suzuki Y
Hong Kong patent HK1155772, 2016.06.10, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
Korea Patent 10-1604502, 2016.03.11, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
Hong Kong Patent HK1161898, 2016.02.26, Tahara H, Suzuki Y, Yamamoto K, Kitahara Y, Suzuki Y
China Patent ZL200980114565.X, 2015.09.16, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H

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EU Patent 2385115, 2015.09.09, Tahara H, Suzuki Y, Yamamoto K, Kitahara Y, Suzuki Y
US Patent 9096878, 2015.08.04, Tahara H, Suzuki Y, Yamamoto K, Kitahara Y, Suzuki Y
Japan Patent 5704753, 2015.03.06, Tahara H, Suzuki Y, Yamamoto K, Kitahara Y, Suzuki Y
Hong Kong (China) patent HK1163739, 2014.11.14, Tahara H, Suzuki Y, Yamamoto K, Kitahara Y, Suzuki Y
Japan Patent 5648912, 2014.10.22, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
US Patent 8653249, 2014.10.11, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
Australia Patent 2009331326, 2014.09.08, Tahara H, Suzuki Y, Yamamoto K, Kitahara Y, Suzuki Y
China Patent. ZL200980157244.8, 2014.05.06, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
Australia Patent 2009218069, 2014.04.16, Suzuki Y, Yamamoto K, Suzuki Y, Tahara H
6) Gene amplification method and use thereof, National University Corporation Hokkaido University
Japan Patent 5688702, 2015.02.06, Chie Nakajima, Yukari Fukushima, Yasuhiko Suzuki
5.2

Application information

1) Japan patent application PCT/JP2019/13132, Novel K95-5901-1 substance and method for producing threof,2019.03.27, National University Corporation Hokkaido University, The Kitasato Institute, Satoshi Omura, Mihoko
Mori, Atsuko Matsumoto, Kazuro Shiomi, Yasuhiko Suzuki, Chie Nakajima, Tomoyuki Yamaguchi.
2) Japan patent application 2018-99704, Novel vectors and use thereof, 2018.05.24, National University Corporation
Hokkaido University, FUSO Pharmaceutical Industries. Ltd, Yasuhiko Suzuki, Miki Nakagawa, Yayoi Kameda,
Takashi Konnai, Tomohiro Okagawa, Naoya Maekawa, Shinya Goto, Yamato Saji, Kazuhiko Ohashi, Shiro Murata, Jo
Kitahara, Keiichi Yamamoto.
3) International patent application 2017-535564, Monoclonal antibody neutralizing infectivity of all ebolavirus species,
2018.2.9, Hokkaido University, Kyowa Hakko Kirin, Co., Ltd., Ayato Takada, Reiko Yoshida, Wakako Furuyama,
Hiroko, Miyamoto, Junki Miyamoto, Shigeru Iida, Shinya Ogawa
4) Japan patent application 2017-071729, Biaryl sulfonamide derivatives that inhibit filovirus entry into cells, 2017.3.31,
Hokkaido University, Ayato Takada, Masahiro Sakaitani, Wakako Furuyama
5) Japan patent application 2015-161567, Monoclonal antibody neutralizing infectivity of all ebolavirus species,
2015.08.19, Hokkaido University, Kyowa Hakko Kirin, Co., Ltd., Ayato Takada, Reiko Yoshida, Wakako Furuyama,
Hiroko, Miyamoto, Junki Miyamoto, Shigeru Iida, Shinya Ogawa
6) Japan patent application 2014-190530, Kits including markers to distinguish drug susceptibility and use thereof,
2014.09.18, Hokkaido University, Rakuno Gakuen University, Kanto Chemical, Co., Inc., Yutaka Tamura, YasuhikoSuzuki, Chie Nakajima, Masaru Usui
6

AwardsNumber of awards: #7

1) William Hall: “Robert C. Gallo Award for Scientific Excellence and Leadership in Medical Virology”, 2019. 6.92) Hiroshi Kida: “Person of cultural merits”, 2017.10.24
3) Hiroshi Kida: “The order of the sacred treasure, gold and silver star”, 2017.4.29

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4) Ayato Takada: “Hokkaido University President’s Award for Outstanding Research”, 2017.1.31
5) Hiroshi Kida: “The Hokkaido distinguished service award”, 2016.10.31
6) Ayato Takada: “Hokkaido University President’s Award for Outstanding Research”, 2016.2.3
7) Ayato Takada: “Hokkaido University President’s Award for Outstanding Research”, 2015.2.23
7

External grants
Number of grants: #3

1) Core-to-Core Program, B. Asia-Africa Science Platforms, (Japan Society for the Promotion of Science), “Research
Exhange toward social implementation of novel diagnosis method based on comprehensive sequencing”, 2019-2022,
7,040,000 JPY, Junya Yamagishi (PI), William Hall and Arnab Pain
2) Tropical Medicine Research Center General Collaborative Research Grant (Nagasaki University), “Applying Linkage
Group Selection to P. falciparum in vitro”, 2017-2018, 300,000 JPY, Axel Martinelli (PI) and Chihiro Sugimoto
3) Grant-in-Aid for Scientific Research (C) (Japan Society for the Promotion of Science), "Long non-coding RNAs inviral infection", 2016-2018, 4,810,000 JPY, Michael Carr (PI) and Hirofumi Sawa
8

Gifts
Number of gifts: #4

1) TheAtlantic Philanthropies Director/Employee Designated Gift Fund (Atlantic Filanthropies), “the Development of
New Methods and Training for the Detection of New Virus Diseases Project”, 2019.9.1, US$150,000, Hirofumi Sawa
2) TheAtlantic Philanthropies Director/Employee Designated Gift Fund (Atlantic Filanthropies),” immune therapy to treat
coronavirus in the very early stages of infection,” 2019.3.31, US$10,000.00, Hirofumi Sawa
3) TheAtlantic Philanthropies Director/Employee Designated Gift Fund (Atlantic Filanthropies),” immune therapy to treat
coronavirus in the very early stages of infection,” 2019.3.31, US$10,000.00, Hirofumi Sawa
4) The Atlantic Philanthropies Director/Employee Designated Gift Fund (Atlantic Filanthropies) “The development of
new methods and training for the detection of new virus diseases”,2018.11.14, €50,000.00 , Hirofumi Sawa
9

Science outreach activities
Number of science outreach activities: #31
The following presentations were made in seminars for the public.

1) Ayato Takada: “Basic preventive measure of the novel coronavirus is to dilute it”, The Hokkaido Shimbun press,2020.3.3 [Newspaper article]
2) Ayato Takada: “Diseases transmitted from animals to humans”, Asahi Shogakusei Shimbun, 2020.2.16 [Newspaper
article]3) Ayato Takada: “Virus is rogue?”, Science book cafe, Yomiuri Shimbun Building, Tokyo, Japan, 2019.9.10 [Science
cafe]

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4) Ayato Takada: “Detection/diagnosis/therapy of Ebola viruses”, JICA Yokohama, Yokohama, Japan, TICAD seminar:
What we can do to fight Ebola virus, a possibility of contribution and challenge of industry, government and academia,
2019.6.16[Open lecture]5) Hirofumi Sawa: “Observation of mosquito larva, pupa and imago. Making the mosquito specimen,” P2 Practical Room,
Research Center for Zoonosis Controol, Hokkaido Universitym Sapporo, Hokkaido University Kids Laboratory 2019,2019.03.25 [Special practicum]6) Junya Yamagishi: “Why are diseases infected?”, Seminar Room, Institute for Genetic Medicine, Hokkaido University,
Sapporo, Hokkaido University Kids Laboratory 2019, 2019.3.25 [Special lecture]7) Hirofumi Sawa: “Zoonosis control measures contributing to One Health,” Conference Hall, Hokkaido University,
Sapporo, Resaerch Center for Zoonosis Control extension course open to the public, 2019.1.12 [Extension course]
8) Yasuhiko Suzuki: “Activities torward the control of Zonosis,” Research Center for Zoonosis Control, Hokkaido
University, Sapporo, SAKURA Exchange Program in Science, 2018.8.6 [Special lecture]9) Keita Matsuno: “Viruses hiding in ticks”, Amami Branch of Kagoshima University Research Center for the PacificIslands, Amami, 2018.3.1 [Open lecture]10) Axel Martinelli: “An introduction to genomics”, Sapporo Higashi High School, Sapporo, Academic Fantasista,
2018.2.2 [Visiting lecture]11) Yasuhiko Suzuki: “Tuberculosis: Never ending threat,” Auditorium, School of Agriculture, Hokkaido University,
Sapporo, Research Center for Zoonosis Control extension course open to the public, 2018.1.20 [Extension Course]12) Michael Carr: “What are viruses?”, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Academic
Fantasista, 2017.12.12 [Open lecture]13) Ayato Takada：“Viral Zoonosis Research in Africa”, JICA Research Institute, Tokyo, SATREPS Workshop, 2017.8.28[Extension course]
14) Lorena Brown: “Preparedness for pandemic influenza” Hotel Mystays Sapporo Aspen, Sapporo, Strategy for theControl of Zoonoses, 2017 7.8 [Open seminar]
15) William Hall: “International contributions to our appreciation of new and emerging virus infections” Hotel Mystays
Sapporo Aspen, Sapporo, Strategy for the Control of Zoonoses, 2017 7.8 [Open seminar]
16) Arnab Pain: “Latest trends in tracking pathogens by genomics” Hotel Mystays Sapporo Aspen, Sapporo, Strategy for
the Control of Zoonoses, 2017 7.8 [Open seminar]17) Keita Matsuno: “Interactive lecture of microbes and their researchers”, The 86th Annual Meeting of the JapaneseSociety of Parasitology, 2017.5.28-29 [Science Cafe]18) Ayato Takada：“Recent Advances in Ebola Virus Research”, Sapporo Convention Center, Sapporo, Infection Control
Doctor Lecture Course, 2016.10.25 [Extension course]
19) Ayato Takada：“Recent Advances in Virology –Topics from Influenza and Ebola–”, Hokkaido High Technology
College, Eniwa, Heisei 28 Bio Lecture for High School Teachers, 2016.8.4 [Extension course]20) Ayato Takada: “Zoonosis –Topics from Influenza and Ebola–”, Hokkaido University, Sapporo, Heisei En-yu Night
School, 2016.8.2 [Extension course]21) Ayato Takada：“Ecology of Viruses”, Hokkaido University, Sapporo, The 58th Hokudaisai Extramural Lecture, 2016.6.4[Extension course]

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22) Ayato Takada: “How do viruses survive?”, Marunouchi building, Tokyo, Keio Marunouchi City Campus RegularSeminar, Sekigaku50, 2015.11.18 [Extension course]23) Ayato Takada: “Ebola virus”, Miyazaki Kanko hotel, Miyazaki, The 5th International Symposium at Miyazaki
University, Preparation for impending infectious diseases, focusing on zoonoses, 2015.11.13 [Extension course]24) Ayato Takada: “Ebola virus research: Current situation and future prospects”, The alumni hall Frate at school of
medicine of Hokkaido University, Sapporo, Science Council of Japan, Second Section Meeting Of The Life Science
Field, Public Academic Lecture, 2015.8.5 [Extension course]25) Ayato Takada: “Recent advance in Ebola virus research”, Conference Hall, Hokkaido University, Sapporo, Hokkaido
University extension course 2015, 2015.7.20 [Extension course]
26) Hiroshi Kida: “Strategy for the control of zoonoses”, Open Hall, School Of Engineering, Hokkaido University, The 1st
GI-CoRE Open Forum, 2015.7.3 [Extension course]27) Ayato Takada: “Ebola hemorrhagic fever, Current situation and future prospects for science research”, Satellite Campus
of Gifu University, Gifu, Gifu University public lecture, 2015.3.2 [Extension course]28) Ayato Takada: “Ebola virus research, Current situation and future prospects”, Fujita Health University, Toyoake,
The200th seminar in medical science, 2014.10.1 [Extension course]29) Ayato Takada: “Ebola hemorrhagic fever and BSL4”, Nagasaki City Library, Nagasaki, Institute of tropical medicine
Nagasaki University, Extension special course open to the public, 2014.9.21 [Extension course]30) Ayato Takada: “Activities of the Hokudai Center for Zoonosis Control in Zambia”, UDX Conference, Tokyo, J-GRID
extension course open to the public, SFTS, MERS, Ebola hemorrhagic fever referred as recent topic of infectious
diseases, 2014.8.23 [Extension course]31) Hiroyuki Oshiumi: “Innate Immune response during viral infection,” Lecture Hall, Graduate School of Veterinary
Medicine, Hokkaido University, Sapporo, Seminar: Infecton, Pathogenesis and Immunity-For the Control of Zoonosis-,
2014.8.20 [Open seminar]
10

Training
Number of trainings: #2

1) Mariko Tanaka, Walter Muleya, Shiho Torii, Dayana Baker, Gabriel Gonzalez, Yongjin Qiu, Kyoko Hayashida, Keita
Matsuno, Yasuko Orba, Ryo Nakao, Junya Yamagishi, Stephen Barker, Yuki Eshita, Sawa Hirofumi, William Hall:“Training course of infection, immunity, diagnosis, and pathogenesis of virus pathogens”, Practical Room, ResearchCenter for Zoonosis Control, Hokkaido University, Sapporo, Japan, 2019. 9.19-10.2
2) William Hall: “Chikungunya virus detection”, Instituto de Medicina Tropical Pedro Kourí, Havana, Cuba, The 15th
International Dengue Course-Challenges of Zika and Chikungunya transmission, 2017.8.12-21
11

Collaborations with institutions (universities, research institutes, local government, companies, etc.) other thanaffiliated universities
Number of collaborations: #31

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1) Department of Molecular Medicine, Mayo Clinic
Dr. Hideki Ebihara (Associate Professor) is collaborating with Unit for Exploration of Pathogens on developmentof detection methods of tick-borne viruses.
2) Joint Faculty of Veterinary Medicine, Yamaguchi University
Dr. Ken Maeda (Professor) and Dr. Hiroshi Shinmoda (Associate Professor) is collaborating with Unit for
Exploration of Pathogens on detections of tick-borne phleboviruses.
3) Research and Development (R&D) Center for Marine Biosciences, JAPAN Agency for Marine-Earth Science andTechnology (JAMSTEC)
Dr. Takuro Nunoura (Deputy Director) is collaborating with Unit for Exploration of Pathogens on development of
sequencing methods of tick-borne virus genome.
4) Asa Zoo, Hiroshima, Japan
Dr. Noriyuki Nonoue (Veterinarian) is collaborating with Unit for Exploration of Pathogens on development ofdetection methods of tick-borne viruses and elephant-specific pathogens.
5) Department of Pathology, Shiga University for Medical Sciences
Professor Kazumasa Ogasawara (Immunology) is collaborating with the Unit for the Development of Vaccines andBiologicals on animal experiments to test vaccine safety and efficacy.
6) Graduate School of Science and Technology, Niigata University
Associate Professor Takashi Abe, who has developed BLSOM, is collaborating with Unit for Pathogen Genomics on
the analysis of horizontal gene transfer in parasites and vectors.
7) Institute of Tropical Medicine, Nagasaki University
Associate Professor Richard Culleton is collaborating with the Unit for Pathogen Genomics on malaria infections andparasite genetic cross.
8) School of Veterinary Medicine, University of Zambia
Professors Aaron Mweene, Bernard Han’gombe and Boniface Namangala are collaborating with the Unit for
Exploration of Pathogens on pathogen detection and characterization from animals and insects in sub-SaharanAfrica.
9) University Teaching Hospital, Zambia
Dr. Mwaka A. Monze is collaborating with the Unit for Exploration of Pathogens on pathogen detection andcharacterization from humans in sub-Saharan Africa.
10) Department of Parasitology, University of Colombo, Sri Lanka
Dr. Sisira Pathirana, is collaborating with on with the Unit for Pathogen Genomics on malaria infections and parasite
genetic cross in monkeys. Collaboration with industrial parties as shown in Fig.1 is also important for influenza
vaccine development.
11) Laboratory of Virology at the Rocky Mountain Laboratories (RML), DIR NIAID, NIH
Dr. Heinz Feldmann and Andrea Marzi are collaborating with the Unit for Exploration of Pathogens on thedevelopment of anti-filovirus therapeutics.
12) Institut National de Recherche Biomédicale
Professors Steve Ahuka, Justin Masumu, Sheila Makiala and Jean-Jacques Muyembe are collaborating with the Unit
for Exploration of Pathogens on the development of rapid diagnosis kits for hemorrhagic fevers.

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13) State Central Veterinary Laboratory, MongoliaDrs. Ulaankhuu Ankhanbaatar, Bodisaikhan Khishgee, Basan Ganzorig are collaborating with the Unit for
Exploration of Pathogens on avian influenza surveillance in Mongolia.
14) Faculty of Veterinary Medicine, Hokkaido University, Japan
Dr. Satoru Konnai (Associate Professor) is collaborating on the development of therapeutic recombinant antibodies.
15) Faculty of Veterinary Medicine, Rakunogakuen University, Japan
Dr. Yutaka Tamura (Professor) and Dr. Masaru Usui (Associate Professor) is collaborating on elucidate the drug
resistance acquisition mechanism by bacterial pathogens.
16) Leprosy Research Center, National Institute of Infectious Disease, Japan
Dr. Tetsu Mukai (Unit Head) is collaborating on development of rapid diagnostic methods for leprosy.
17) Japan BCG Laboratory, Japan
Dr. Kazuhiro Matsuo (Division Director) is collaborating on the genome analysis of Mycobacterium bovis BCG frompatients.
18) Osaka Institute of Public Health, Japan
Dr. Aki Tamaru (Senior Research Officer) is collaborating on the molecular analysis of multi- and extensively drug
resistant Mycobacterium tuberculosis clinical isolates.
19) Fuso Pharmaceutical Industries, Ltd., Japan
Dr. Keiichi Yamamoto (Deputy Division Director), is collaborating on the development of therapeutic recombinant
antibodies.
20) Tohoku Bio-Array Co., Ltd., Japan
Dr. Mitsuo Kawase (Division Director), is collaborating on the development of rapid, simple and low-cost drug
susceptibility test for tuberculosis.
21) Philippine Carabao Center, Department of Agriculture, The Philippines
Dr. Claro Mingala (Director of Biotechnology Center) and Dr. Marvin Villanueva (Section Head) are collaboratingon the surveillance of drug resistant enterobacteria and leptospirosis.
22) National Institute of Health, Ministry of Public Health, Thailand
Dr. Benjawan Phetsukusiri (Section Director) is collaborating on the molecular analysis of multi- and extensively
drug resistant M. tuberculosis clinical isolates in Thailand.
23) Faculty of Public Health, Mahidol University, Thailand
Dr. Fuangfa Utrarachkiji (Head Department) is collaborating on the surveillance of drug resistant enterobacteriaceae
in Thailand.
24) Faculty of Public Health, Thammasat University, Thailand
Dr. Kanjana Changkaew (Lecturer) is collaborating on the surveillance of drug resistant enterobacteria in Thailand.
25) Department of Medical Research, Ministry of Health and Sports, Myanmar
Dr. Khin Saw Aye (Deputy Director General) is collaborating on the molecular analysis of multi- and extensively
drug resistant Mycobacterium tuberculosis clinical isolates in Myanmar.

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26) German-Nepal Tuberculosis Project, Nepal Anti-tuberculosis Association, Nepal
Mr. Bhagwan Maharjan (Head of Laboratory) is collaborating on the molecular analysis of multi- and extensively
drug resistant Mycobacterium tuberculosis clinical isolates and zoonotic infection of M. tuberculosis complex in
Nepal.
27) Faculty of Medicine Peradenia University, Sri Lanka
Dr. Chandika Gamage (Senior Lecturer) is collaborating on the molecular epidemiology of tuberculosis in Sri Lanka.
28) The University Teaching Hospital, The Ministry of Health, Zambia
Dr. Grace Mbulo (Head of Laboratory) and Mr. Eddie Solo (Senior Medical Scientist) is collaborating on themolecular analysis of multi- and extensively drug resistant Mycobacterium tuberculosis clinical isolates in Zambia.
29) Zambia Tuberculosis and Leprosy Trust
Ms. Charity Habeenzu (CEO) is collaborating on the survey of leprosy in Zambia.
30) The University of Zambia, Zambia
Dr. Bernard Hang’ombe (Professor) is collaborating on the zoonotic infection of M. tuberculosis complex in Zambia.
31) South Valley University, Egypt
Dr. Hassan Diab (Lecturer) is collaborating on the molecular epidemiology of tuberculosis in Egypt.
● Issues affecting the research and measures to overcome these/future developments
Currently, the global station does not face any major issues.
In addition to core funding from MEXT, the global station is supported by other funding, such as, Japan Initiative for
Global Research Network on Infectious Disease (The Japan Agency for Medical Research and Development “AMED”)
and the International Collaborative Research Program for Tackling the NTDs (Neglected Tropical Diseases) Challenges inAfrican countries (AMED). These funding sources have greatly supported overseas activity of the Research Center for
Zoonosis Control, especially in Zambia, which provides significant resources to GI-CoRE, such as, materials for pathogen
detection and characterization in tropical animals. Seamless interoperability of these resources and funding will bebeneficial to all GI-CoRE affiliated members. In addition, technical assistance for enhanced capacity building for these
institutions in developing counties will be an important task of GI-CoRE.
Researchers from the foreign universities who are based at Hokkaido University are eligible to apply for Japanese
grants, such as “Kakenhi (Grant-in-Aid for Scientific Research)”. Well-organized and sustainable support for theirapplications by Japanese academic staff will be needed, because their project schemes including accounting regulations aredifferent from those in the EU and USA. Technical staff at the Research Center for Zoonosis Control are insufficient tosupport GI-CoRE activities, including DNA/genome analysis, cell imaging, and bioinformatics. Hokkaido University isrequired to address this staffing shortage.

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2. Education (Graduate Schools to Foster Global Human Resources)
2.1

Establishment of a new graduate school; Graduate School of Infectious Diseases● Background
The threat to economies and societies has significantly increased due to emerging and re-emerging infectious diseases
and trans-boundary infectious diseases, such as the global spread of Ebola hemorrhagic fever, the SARS and MERS
coronaviruses, and Zika fever. Domestic and international demand for increased research efforts into combatting infectious
diseases, including development of control measures, has significantly increased. In order to maintain the health anddevelopment of humanity, outbreaks of zoonotic diseases demand an understanding of the health of animals and theirecosystems. There is therefore an urgent need to provide human resources which can respond immediately to new andemerging infectious diseases. An international deployment of human resources working towards the concept of “One Health”
is and will continue to grow as human societies further encroach on wildlife habitats.
A culture of One Health will require the establishment of a robust framework for higher educational institutions. Wellbalanced and carefully formulated educational schemes should provide the fundamentals of immunology, molecularbiology and genomics which must be integrated with a program of applied sciences, including clinical microbiology,
vaccinology, epidemiology and the practical skills necessary for diagnoses, prevention and treatment of disease at epidemicsites.
Integration and systemization of educational resources and the establishment of a new educational systems with a viewto utilizing the human resources necessary for One Health are challenges facing our university. The number of educatorsand researchers working in the fields of infectious diseases at institutions in Japan, however, continues to decrease with abias towards allocation of resources to scientific fields other than the study and control of zoonoses. It is therefore not astraightforward matter to establish the systems that are necessary for responding rapidly to the global threats to humanhealth. The situation is further complicated because the origins of these infectious diseases are located mostly in developing
countries in tropical and sub-tropical zones and there is no currently sustainable initiative for capacity and infrastructurebuilding in these countries.

These are urgent social needs and they require an education system which transcends

conventional academic field barriers to provide specialists with a truly internationally-oriented One Health mindset.
Since 2010, the Graduate School of Veterinary Medicine, Hokkaido University has run the Program for Leading
Graduate Schools: Fostering Global Leaders in Veterinary Sciences toward Contributing to “One Health” and has initiatedthe development of human resources to this end. In order to strengthen and expand this educational scheme forpostgraduates, Hokkaido University established the “Graduate School for Infectious Diseases” in 2017 (Appendix 1).
The detailed information on the current program for leading graduate schools can be found at the following link:
https://www.infectdis.hokudai.ac.jp/en/
2.2

Vision for fostering human resources at the proposed Graduate School of Infectious Diseases
An important task for the new Graduate School is to produce experts who will take on leadership roles in the prevention

and control of infection as an increasing social problem. The School’s aim is to produce graduates:

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”1) who have an academic, i.e. evidence-based background but who have a broad vision and practical skills in infection,
immunity, epidemiology and related disciplines.
2) who can provide leadership across national boundaries to implement the One Health concept.
3) who hold Ph.D. level qualifications in infectious diseases or veterinary medicine.
Well-organized and systemic curriculum, including the interaction with the international health community throughthe “Internship Abroad” program at the Graduate School, which is designed to meet the above-mentioned missions anddevelopment of human resources (Appendix 2). Students can pursue either of two tracks in course studies towards a Ph.D.
in infectious diseases or veterinary medicine. Actual number of enrollment at the Graduate School of Infectious Diseases
is 14 in 2017 and 16 in 2018 and is exceeding the admission quota.
2.3

Educational affiliation with the GI-CoRE
A number of members appointed at GI-CoRE have already been participating in the education program at the new

Graduate School. These members are recognized at the national and international level as experts in the fields defined above
and together will provide a level of education that will provide the necessary skill sets for the next generation of One Healthpractioners (Appendix 3).
One of essential components of the new Graduate School will be globalization and to this end discussions areunderway with the Graduate School of Veterinary Medicine of University College Dublin with a view to establishing a
joint, or cotutelle (co-tutoring), Ph.D. degree. In preparation for this joint program both parties have been conducting
exchange of faculty, staff and students since 2014.
Students of the Graduate School of Veterinary Medicine and Graduate School for Infectious Diseases (2017~) at
Hokkaido University attended the lecture “Advances in Infection Biology” which has been held in University College
Dublin since 2016 and professors of Hokkaido University delivered lectures on topics realting to zoonotic diseases andbioinformatics in the same course (Appendix 4). In addition, Hokkaido University invited graduate students from
University College Dublin to Hokkaido University for two-three months and supervised their research topics. Based on
their research at CZC, two co-authored papers in international, peer-reviewed journals have been produced (Appendix 5),
which constitute an essential part of their thesis. Furthermore, UCD has secured an EU grant for graduate education,
ERASMUS, to invite our faculty staff and graduate students. These bidirectional relationships can further strengthen
educational links toward the establishment of the cotutelle/joint degree program.
Finally, researchers from each of the international units of the GI-CoRE who are based at Hokkaido University sharethe laboratories with young researchers and students on a daily basis engaging in collaborative research. These interactions
also contribute to the improvement of English language skills for Japanese and overseas students from non-English
speaking countries through seminars which provide skills for English oral presentations and writing. As the results of theiracademic interactions, several co-authored publications have already been produced (Appendix 6).
Since 2016, at the Summer Institute held at the Sapporo Campus, a faculty professor from University College Dublin
delivers lectures on “Bioinformatics and Computational Biology” (Appendix 7), which attracted international as well asJapanese students from a wide range of academic backgrounds. Therefore, GI-CoRE also extends its activity to support
globalization of the graduate and undergraduate education at Hokkaido University.

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3. Establishment of Framework
3.1

Management System
The Global Institution for Collaborative Research and Education (GI-CoRE) was established in April 2014 as a facultyorganization under the direct control of the Hokkaido University President, with the aim of promoting international
collaborative research and education that leverages Hokkaido University’s strengths and distinctive character. GI-CoRE is
positioned as an independent educational and research organization managed by the President as its director. It brings
together world-class teaching staff from around the world, within Japan and within Hokkaido University, based on a new
idea to invite the world highest level research units. GI-CoRE’s framework enables the conduct of international
collaborative research and education systematically together with leading research units invited from overseas, rather thanrelying on international exchange promoted individually by researchers. Implementing this unprecedented way to accept
overseas researchers, Hokkaido University reformed the management system and established the framework of GI-CoRE
promptly under the President’s powerful leadership. GI-CoRE appointed the President as the director, and Vice President
for International Affairs as the deputy director. Under the President/GI-CoRE director, the GI-CoRE steering committee isestablished to discuss matters important to GI-CoRE and comprises the President, Vice Presidents for International Affairs
and for Planning and Management, and faculty deans/research center directors who are appointed to serve as members to
the committee in turn. The steering committee was held a total of 14 times, between April 2014 and March 2018, anddiscussed the following: 1) Matters regarding the personnel transfers of faculties; 2) Matters regarding the establishment,
reform or termination of global stations; 3) Matters regarding the evaluation of the research and educational activities ofglobal stations; 4) Matters regarding budgets; and 5) Other important matters pertaining to the administration of GI-CoRE,
such as progress reports. To promote the collaborative research and education that capitalizes upon the distinctive
characteristics of the university from a practical viewpoint, Hokkaido University place global stations (GSs) in GI-CoRE.
Each GS has a designated station director who shall be one of the core teaching staff in the research field. Invited worldleading overseas research units are assigned to the GS so as to foster the promotion of international collaborative researchand education together with the leading teaching staff within the university.
Member List of the Steering Committee *As of 1 April 2018
Name
1

2
3
4
5

Toyoharu NAWA
Masanori
KASAHARA
Jyunji NISHII
Fumihiko
YAMAMOTO
Koichiro ISHIMORI

Affiliation 1

Affiliation 2
Director, Global Institution for

President

Collaborative Research and Education
Deputy Director, Global Institution

Executive / Vice President

for Collaborative Research and
Education

Executive / Vice President
Dean / Professor, Graduate School ofLetters
Dean / Professor, Faculty of Science12820-090190.indd 128

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6

Dean / Professor, Faculty of Health
Sciences

Toshiyuki

Director / Professor, Research

NAKAGAKI

Institute for Electronic Science8

Hiroki SHIRATO

Professor, Faculty of Medicine

9

Hirofumi SAWA

10

Takashi INOUE

11

Jian Ping GONG

7

Professor, Research Center for
Zoonosis Control
Professor, Research Faculty ofAgriculture
Professor, Faculty of Advanced Life
Science

Yoshikazu

Professor, Graduate School of

MIYANAGA

Information Science and Technology

13

Natsuhiko OTSUKA

Professor, Arctic Research Center

14

Ko HASEGAWA

15

Ryuichiro SHIMA

12

3.2

Takeshi SAITO

Director, Global Station for Quantum
Medical Science and Engineering
Director, Global Station for Zoonosis
Control
Director, Global Station for Food,Land and Water Resources
Director, Global Station for Soft
MatterDirector, Global Station for Big Data
and Cybersecurity
Director, Global Station for Arctic
Research

Executive / Vice President
Director, International Affairs
Department

Establishment and Improvement of Acceptance System/Environment, and Future Prospects, etc.
Under the governance of the President, GI-CoRE has established the necessary system to accept overseas researchers

and improved the environment to operate GI-CoRE tasks, as follows, in order to invite the world’s top research units fromexternal universities and institutions, and allow them to collaborate with the fine teaching staff in the related disciplines of
the university.
1) GI-CoRE introduced the cross-appointment system with overseas universities and institutions before the system
was implemented by the whole university. The cross-appointment system is to appoint top-class researchers fromoverseas and domestic institutions at Hokkaido University, while keeping their status at the host institutions andpay salaries to them based on the level of the effort at Hokkaido University.
2) The implementation of cross appointment system has produced more flexible personnel and salary system for theoverseas faculty members such as choosing the annual salary system, relaxing the employment age restriction, andestablishing a new title Distinguished Professor which shall be awarded in recognition of particularly importantachievement in their fields of study.
3) For the overseas researchers who conduct education and research activities at Hokkaido University, GI-CoRE has
set up a flexible system on travel expense and accommodation rental.
4) To utilize the exiting research resources in the university, GI-CoRE has also applied the cross-appointment system
to the participating researchers of Hokkaido University who conduct international collaborative research andeducation, and appointed them to the positions both in their original departments and in GI-CoRE.

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5) Upon conducting advanced international collaborative research and education, GI-CoRE has reviewed the pointbased personnel system and applied flexible personnel distribution even in positions for researchers.
6) To secure the academic environment to concentrate on research, GI-CoRE faculty members are exempt fromadministrative tasks such as faculty meetings, etc.
The above-mentioned cross-appointment system, annual salary system for regular teaching staff and other relevant
systems have been started as a pilot system for the other departments within the university. Other than the systems, GICoRE has provided rich research environments and extensive educational experiences to young researchers, and led togood effects as fusion of different research fields/interdisciplinary collaboration with diversified departments to cooperate
in the project.
Through this virtuous cycle, the pilot systems at GI-CoRE have been gradually expanded to the whole university, andhave started to reinforce the university’s administrative function.
From now on, GI-CoRE will utilize the established network and achieved outcomes of collaborative research withinstitutions/organizations in order to further strengthen research projects which give the university a certain superiority overother research universities, and implement ‘global postgraduate-level education by organic fusion of different fields’ atgraduate schools of related fields. For this promotion, besides the management expenses grants from the Japanese
government, GI-CoRE aims to obtain various funds such as competitive funds as grants-in-aid for scientific research anddonation, etc.
3.3

Administrative System
In order to support research and educational activities in each global station, administrative staff are required tostrengthen their capabilities to handle international affairs. Considering this, Hokkaido University has set up a GI-CoREspecialized administrative section in the International Affairs Department, distributed staff members with study/work
abroad experiences to the section, and established bilingual (English) administrative support systems. Also, bilingual staff
have been stationed in each global station office to support daily research activities conducted there.

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12

Enrollment
capacity

Established Research Center for Zoonosis
Control in 2005
Conducted research of zoonosis control in the
21st Century COE program and global COE
programCreation of new research field from medical
science, veterinary medical science, andinformation science
Conducting a “One Health” Program for Leading
Graduate Schools from 2011 to foster global
leaders for zoonosis control

Our past achievement

Emerging and re-emerging infectious diseases areappearing worldwide
Infectious diseases; such as Ebola
hemorrhagic fever, pandemic influenza,
dengue fever, MERS coronavirus havebecome a major public health concern.
Lack of expertise and an absence of systematic
educational training schemes
Insufficient basic research of ecology,
pathogenicity and transmission routes ofzoonotic pathogens.
There is an urgent need for the development
of diagnostic, preventive and therapeutic
methods to better tackle zoonoses.
A lack of experts in the control of zoonotic
diseases with relevant academic backgrounds.

Urgent Need for Zoonosis Expertise

Major: Infectious Diseases

Graduate School of
Infectious Diseases

Established in April 2017
Degree to be awarded

Two types of degree provided in accordance with specialization
Enrolment of students who have various academic backgrounds
including relevant academic fields other veterinary medicine andmedicine at the Graduate School of Infectious Diseases.
The Graduate School covers a wide range of advanced subjects.
The Graduate School grants a degree of Ph.D. (Infectious Diseases) or
Ph.D. (Veterinary Medicine).

Development of experts for zoonosis control
The School certifies students expertise (Zoonosis
Control Expert, ZCE) based on the following criteria:
practical experience in countries where infectious
zoonotic diseases spread, research achievements andacademic credits in relevant subjects.

Top level world scientists from the
University of Melbourne and University
College Dublin as research supervisors.
Improvement of scientificcommunication skills in English.

Collaboration with world-class leading organizations

Supervision by leading professors in the relevant fieldsof microbiology, immunology and infectious diseases.
Interdisciplinary learning in areas, such as,
bioinformatics, mathematical modeling and risk
analysis of infectious diseases.
Support for internship overseas that aims to develop
career paths at a global level.
Development of practical skills in disease endemic spots.
Access to state-of-the art research facilities/equipment.

Development of practical skills activated on the international stage

Advanced education systems and unique curriculum

Doctor of Philosophy in Infectious Diseases
4 years Doctor of Philosophy in Veterinary Medicine

Courseterms

Education
Appendix 1

Universities and research institutes in Japan andoverseas in academic areas of veterinary medicine,
microbiology, immunology, epidemiology etc.
Government organization, such as, Ministry ofAgriculture, Forestry and Fisheries etc. in Japanand overseas.
International organizations which are responsiblefor infectious disease control in animals and foodproduction and safety such as OIE, FAO.

Ph.D.（Veterinary Medicine) degree holders

Universities and research institutes in Japan andoverseas in academic areas of infectious diseases,
public health, tropical medicine etc.
Government organizations e.g. Ministry of Health,
Labor and Welfare, Ministry of Agriculture,
Forestry and Fisheries in Japan and overseas.
International organizations which are responsiblefor international health control, such as WHO.

Ph.D.（Infectious Diseases) degree holders

Career Path

Degrees are awarded to doctoral candidates whomeet the following criteria:
They have demonstrated an advanced
knowledge and skills for the study of infectious
disease and related subject areas and canpractically apply this knowledge to practicalresearch and control measures.
Who have shown leadership on the international
stage to implement a “One Health” policy for the
improvement of the health of humans, animals
and their environments.

Diploma policy

Schools and Institutes in charge

GI-CoRE

Graduate School of Medicine

Research Center for Zoonosis Control

Graduate School of Veterinary Medicine(仮称)
Graduate
School of Infectious Diseases, Hokkaido University

20-090190.indd 132

Thesis Defense

Internship at overseas field (such as epidemiological investigation
at the on-site field), universities, research institutions,international governmental organizations, etc.

Internships Abroad B (2 credits）

Theme of the dissertation
Transboundary pathogens, Development of method of
prevention and diagnosis, Fundamental research ofpathogenicity etc.

Research on Infectious Diseases IIB（8 credits）

Year 3・4

Core Subjects on Infectious Diseases IIB（a minimum of ２credits）

Advanced Lecture on Pathology of Infectious Diseases
Advanced Lecture on Transboundary Diseases
Advanced Lecture on Pharmaceutical Development

Year 2

Advanced Seminar on Infectious Diseases (2 credits）
Advanced Lecture on Pathogen Genomics, Advanced Lecture on Zoonosis Control,
Advanced Lecture on Biological Defense

Research on Infectious Diseases I （8 credits）

Required subjects for acquiring
Ph.D. in Infectious Diseases

Common Course

Required subjects for acquiring
Ph.D. in Veterinary Science

Research Ethics Seminar（１ credit)/Academic English（２credits）

Advanced Lecture on Biostatistics, Practice on Analytical Machines, Advanced Lecture on Information Science,
Advanced Lecture on Immunology, Advanced Lecture on Parasitology, Advanced Lecture on Veterinary Public Health,
Advanced Lecture on Microbiology, Advanced Lecture on Veterinary Hygiene

Subjects on Fundamental Veterinary Science and Infectious Diseases（a minimum of ６credits）

Recommended：Basic Medicine, Basic clinical MedicineⅠ（Inter-Graduate School Class）

1st Quality Examination (QE): Career path inquiry, Academic advice

Advanced and Comprehensive Studies on Zoonosis Control (5 credits)

Core Subjects on Infectious Diseases I（a minimum of 2 credits）

Recommended：Medical ethics（Subject of Graduate School of Medicine）
Practice on Epidemiology I（Inter-Graduate School Class）

Academic and career counseling

Advanced Lecture on Risk Analysis
Advanced Seminar on One Health
Advanced Lecture on Mathematical Biology of Infectious Diseases

Core Subjects on Infectious Diseases IIA (a minimum of 2 credits）

2nd QE: Mid-term dissertation evaluation, Decision of the degree title

Internship at international organizations for health andinfection control (WHO etc)

Internships Abroad A (2 credits）

Theme of the dissertation
Infectious diseases, Infection control, Simulation model
for infectious diseases etc.

3rd QE: Preliminary screening of the dissertation～Zoonotic diseases, Transboundary
Animal Infection, Animal diseases, Pathogen,
Vital reaction, Diagnosis/Treatment etc.

Red Frame:
Required

Pathobiology and Preventive Medicine of
Infectious Diseases

Ph.D. in Veterinary
Medicine/ZCE

Blue Frame:
Elective

Education
Final
Report2
Education 22
Appendix

Universities and Institutions worldwide （Veterinary Medicine・Microbiology・Epidemiology ・ Government Office（MAFF, etc.） ・International Organizations （FAO,OIE, etc.）

Certification Examination for Zoonosis Control Expert(ZCE)

Research on Infectious Diseases IIA (8 credits）～Simulation, Risk Analyses, Control
Measures, Management, etc.

Management of Disease Control inInternational Settings

Ph.D. in Infectious
Diseases/ZCE

Universities and Institutions worldwide （Infectious Diseases・Public Health・
Tropical medicine・Veterinary Medicine）, Government Office（MHLW, etc..）・
International Organizations （WHO, OIE, etc.）

Curriculum of PhD/ZCE course in Graduate School of Infectious Diseases

Advanced Seminar on Infectious Diseases (2 credits)
Laboratory seminar
Research progress report.

Research on Infectious Diseases I （8 credits）

Laboratory seminar
Research progress report.

Year 1132

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Ph.D. in Veterinary Science

July 2018 ~1. Infectious diseases and antibiotics (HIGASHI, IGARASHI)- Anti-viral, bacterial and fungal agents- Anti cancer drugs
2. Infectious diseases and vaccines (JACKSON)
3. Molecular modeling to develop new drugs (IGARASHI)- Drug modeling from protein structures- Design of chemical compounds
4. Drug delivery systems (HIGASHI)
5. Drug development and clinical trials (HIGASHI)
6. Exercise and presentation (HIGASHI)

Pharmaceutical development

1. Microbial infection and host responses (HIGASHI, BROWN, CHUA)- Bacterial infection- Virus infection- Parasitic infection- Immune system and inflammation
2. Infection prophylaxis with host defense systems (BROWN)
3. Microbial evasion mechanisms from host defense systems (HARTLAMD)
4. Exercise and presentation

Host responses to microbial infection

University of Melbourne
Prof. David JacksonProf. Lorena Brown
Prof. Elizabeth Hartland
Assist. Prof. Brendon Chua

Lectures at the Graduate School of Infectious Diseases

Ph.D. in Infectious Diseases

Education
Final
ReportEducation 3
Appendix

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No. ofstudents
9
3
7

Fiscal
Year

2015

2016

2017

3 (2)

4 (2)

5 (2)

Academic staff fromHU (No. of Lectures)

GI-CoRE-based Student exchange 1
Education
Final
ReportEducation 4
Appendix135

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2

2

2

1

2014

2015

2016

2017

2 months

3 months

3 months

5 daysExchange
PeriodGI-CoRE Professors

Education
Final
ReportEducation 5
Appendix

Gonzalez G, Sasaki M, Burkitt-Gray L, Kamiya T, Tsuji NM, Sawa H, Ito K. An optimistic
protein assembly from sequence reads salvaged an uncharacterized segment of mouse
picobirnavirus. Sci Rep. 2017 Jan 10;7:40447.
Donovan PD, Gonzalez G, Higgins DG, Butler G, Ito K. Identification of fungi in shotgun
metagenomics datasets. PLoS One. 2018 Feb 14;13(2):e0192898.

UCD Graduate student

Training outcomes (co-authored publications)No. ofstudents

FiscalYear

GI-CoRE-based Student exchange 2

136

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Graduate student

GI-CoRE non-Japanese members

Anindita PD, Sasaki M, Nobori H, Sato A, Carr M, Ito N, Sugiyama M, Orba Y, Sawa H: “Generation ofrecombinant rabies viruses encoding NanoLuc luciferase for antiviral activity assays.”, Virus Res,
215,121-8(2016)

Wada Y, Orba Y, Sasaki M, Kobayashi S, Carr MJ, Nobori H, Sato A, Hall WW, Sawa H: “Discovery of anovel antiviral agent targeting the nonstructural protein 4 (nsP4) of chikungunya virus”, Virology,
505, 102-112(2017)

Phongphaew W, Kobayashi S, Sasaki M, Carr M, Hall WW, Orba Y, Sawa H: “Valosin-containing
protein (VCP/p97) plays a role in the replication of West Nile virus”, Virus Res, 228, 114-123(2017)

Sasaki M, Anindita PD, Phongphaew W, Carr M, Kobayashi S, Orba Y, Sawa H: “Development of a
rapid and quantitative method for the analysis of viral entry and release using a NanoLuc luciferase
complementation assay”, Virus Res, 243, 69-74 (2018)

Sasaki M, Anindita PD, Ito N, Sugiyama M, Carr M, Fukuhara H, Ose T, Maenaka K, Takada A, Hall WW,
Orba Y, Sawa H: “Heparan sulfate proteoglycans serve as an attachment factor for rabies virus entry
and infection”, J Infect Dis, in press (2018)

Torii S, Orba Y, Hang'ombe BM, Mweene AS, Wada Y, Anindita PD, Phongphaew W, Qiu Y, Kajihara M,
Mori-Kajihara A, Eto Y, Harima H, Sasaki M, Carr M, Hall WW, Eshita Y, Abe T, Sawa H: “Discovery of
Mwinilunga alphavirus: a novel alphavirus in Culex mosquitoes in Zambia”, Virus Res, pii: S01681702(18)30098-4. doi: 10.1016/j.virusres.2018.04.005. [Epub ahead of print](2018)

Co-authored publications
Education
Final
ReportEducation 6
Appendix

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Education
Final
ReportEducation 7
Appendix2017 : 44 students enrolled (21 international students from 11 countries） Program Overview
As a part of the future reform strategy towards the 150th
anniversary of Hokkaido University (HU), the university
launched the Hokkaido Summer Institute (HSI) in 2016, utilizing
the climatic advantage of the summer in Hokkaido which iscooler than any other regions of Japan. HSI is a program thatbrings together leading researchers, with proven educationaland research track records, from around the world andprovides courses in collaboration with HU faculty members. In
2018, more than 160 researchers from over 110
universities/research institutes from all over the world will
gather at HU.
HSI enables participants to expand their knowledge of subjects
in cutting-edge research fields at HU that previously were open
only to students of the university. Program participants have an
opportunity to attend classes that employ attractive
educational techniques, such as, field training in Hokkaido’s
extensive land resources and active learning activities, so as todevelop into professionals capable of thriving on the worldstage.
All instruction at HSI is in English. This provides international
students with a stress-free learning environment without
having to worry about language barriers, and also creates a
special opportunity for Japanese students, who can audit
classes taught by internationally acclaimed researchers. The
university strongly hopes that HSI students will cultivate abetter understanding of other cultures and improve theirEnglish-language proficiency and communication skills throughexchanges with researchers and students from other countries.
Off-campus events and field trips are also planned soparticipants can enjoy Hokkaido’s beautiful summer.

Bioinformatics and Computational Biology

Summer Institute138

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References

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Global Institution for Collaborative Research and Education (GI-CoRE)
Final Evaluation for the Global Station for Quantum Medical Science andEngineering/Global Station for Zoonosis Control projects
1. Aims
The Global Institution for Collaborative Research and Education (GI-CoRE) shall implement an
external evaluation of the research, education and organizational framework of the Global Station for
Quantum Medical Science and Engineering/Global Station for Zoonosis Control projects which started
on April 1, 2014. As the projects have welcomed the final (fifth) year of the implementation period
upon the Fiscal Year 2018, the feedback of this evaluation shall be used to decide whether or not torenew the Global Station project for a further period and improve operations upon the renewed period.
2. Evaluation Structure
A "Hokkaido University Global Institution for Collaborative Research and Education External
Evaluation Committee" shall be established in each of the Quantum Medical Science and Zoonosis
Control Global Stations in accordance with the External Evaluation Implementation Guidelines for the
Hokkaido University Global Institution for Collaborative Research and Education Global Station(Document 2). All evaluations and reports shall be undertaken in English.
□ Global Station for Quantum Medical Science and Engineering External Evaluation Committee
Candidates from Quantum Medical Science GS: 2 foreign members, 1 Japanese member□ Global Station for Zoonosis Control External Evaluation Committee
Candidates from Zoonosis Control GS: 2 foreign members, 1 Japanese member*When the evaluation is complete, the GI-CoRE Steering Committee shall receive a report from theCommittee chair.
3. Evaluation Method□The External Evaluation Committee shall check the contents of the Research Progress Report(Document 3) sent in advance from HU before implementing the on-site investigation, and shallevaluate the evaluation items prescribed in Document 4.
□A 5-level evaluation ratings (S to D) and comments shall be obtained for each "Evaluation Item".
Evaluation
Evaluation Explanation
Ratings
S
Achieved outcomes surpassed the original plan (Outstanding)A
B
C
D

Good progress has been maintained and expected outcomes havebeen achieved (Excellent)
Most expected outcomes have been achieved with some slight delays(Good)
Although certain outcomes were achieved, overall results wereinsufficient (Satisfactory)
No expected outcomes were achieved (Unsatisfactory)

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4. Required Expenses
Travel expenses and honorarium shall be provided to the Evaluation Committee Members (inaccordance with HU regulations). Other expenses required for the External Evaluation (as travel
expenses, honorarium, evaluation report printing expenses, etc.) shall be funded by the budget (nonpersonnel cost) of each Global Station.
5. Publishing of Evaluation Results
Evaluation of this project shall be broadly announced, with the results both published on the relevant
HU websites and published as booklets which are sent to external organizations such as the Japanese
Ministry of Education, Culture, Sports, Science and Technology.

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GI-CoRE Global Station External Evaluation ScheduleYear and Month

AgendaFiscal Year 2017 (2017)

August to November
December

Proposal of Evaluation Items and Evaluation Structure (Draft Fixed)
GI-CoRE Steering Committee #13>> Fixing overviews of evaluation items, evaluation structure, schedule, etc.
>> Starting to create the GI-CoRE Research Progress Report (in English)
Selection/Arrangement of the Evaluation Committee Members*Criteria: 2 foreign and 1 Japanese members(candidates who can conduct evaluation in English)*Confirmation of affiliation, main achievements, contact details, etc.

March

GI-CoRE Steering Committee #14>> Fixing the Evaluation Committee Members and evaluation forms>> Official appointment request (by letters from the GI-CoRE Director)

Fiscal Year 2018 (2018)

April

Commencement of the Appointment as the Evaluation Committee
Members

May to June

Completion of the Research Progress Report (in English)>> Forwarding the report to the Evaluation Committee Members for their
document screening

July to August

October

On-site Investigation (by the External Evaluation Committee)
July 19 -20 (for GSZ)
August 8 (for GSQ)
Submission of the Report of the Final Evaluation>> Evaluation Committee Members shall forward their reports of the final
evaluation, based on the document screening and on-site investigation

GI-CoRE Steering Committee #18>> Report of the Final Evaluation by each Chair of the External Evaluation
Committees of GSQ/GSZ on behalf of the three External Evaluation
Committee Members>> Decision of the GSQ/GSZ projects period extension until FY 2019
Fiscal Year 2019 (2020)

March

Expiration of the GSQ /GSZ projects under the GI-CoRE system

Fiscal Year 2020 (2020)

April

Internalization of the GSQ /GSZ projects into the affiliated faculty andcenterJuly

Publication of the Final Evaluation Reports (in English)

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Hokkaido University
Global Institution for Collaborative Research and Education (GI-CoRE)
External Evaluation Implementation Guidelines for the Global Stations
December 15, 2015
Establishment of the Global Institution for Collaborative Research and Education Steering Committee
1. Purpose
These implementation guidelines shall provide the necessary matters for the
implementation of evaluation of the Global Station by non-University affiliated persons(hereinafter the “GS External Evaluation”) of the Hokkaido University Global Institution for
Collaborative Research and Education (GI-CoRE).
2. Committee(1) The "Hokkaido University Global Institution for Collaborative Research and Education
External Evaluation Committee (hereinafter the "Committee")" shall be established by GICoRE in order to perform the matters prescribed in each of the following items.
(i) Implementation of GS External Evaluation(ii) Matters related to the creation and publishing of the report pertaining to the GS
External Evaluation(2) A Committee shall be established for each Global Station that is target for external
evaluation.
3. Composition(1) The Committee shall be composed of third parties other than constituent members of
Hokkaido University, and designated by the Director of GI-CoRE from persons prescribedin each of the following items.
(i) Person designated by the Director of GI-CoRE who is an expert both within and outside
Japan in the research field of the Global Station to be externally evaluated(ii) Persons whom the Director of GI-CoRE deems necessary(2) The Committee members prescribed in the preceding paragraph shall be commissionedby the Director of GI-CoRE after approval by the GI-CoRE Steering Committee.
4. Term of Office(1) The term of office for Committee Members shall be 1 year. However, if a Committee
Member vacancy occurs, the term of office of the successor shall be the remaining term of
the predecessor.
(2) Committee Members may be reappointed.
5. Committee Chair(1) A Committee Chair shall be appointed and selected through mutual election by theCommittee members.
(2) The Committee Chair shall call a Committee meeting as required, and shall chair the said
meeting.

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6. Proceedings(1) A Committee meeting may not be held unless a majority of the members are present.
(2) Committee meeting proceedings shall be decided by a majority of the attending members.
In case of a tie, the Committee Chair shall decide the issue.
7. Implementation of GS External Evaluation(1) The Committee shall implement the GS External Evaluation as prescribed in thefollowing Article.
(2) The Committee may hear the opinions of persons concerned and implement firsthandinvestigations related to the implementation of the GS External Evaluation.
8. Evaluation Items
The Committee shall evaluate the items prescribed by GI-CoRE in each of the following
items.
(1) Items related to research(2) Items related to education(3) Items related to the structure of the research and education center(4) Other items deemed necessary by the Committee
9. Creation and Publishing of the Report
The Committee shall collate the evaluation results prescribed in the preceding paragraphand publish the results in a report.
10. Response to Evaluation Results
The Director of GI-CoRE shall promptly work to implement improvements in view of thereport prescribed in the previous paragraph for items in which improvements are deemednecessary.
11. General Affairs
General affairs for the Committee shall be processed by the Division of International
Relations, International Affairs Department.
12. Miscellaneous Provisions
Necessary matters concerning GS External Evaluation other than those prescribed withinthese implementation guidelines shall be prescribed separately by the GI-CoRE Steering
Committee.
Supplementary Provisions
These guidelines shall come in force on 12 December 2017.

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REGULATIONS FOR THE HOKKAIDO UNIVERSITYGLOBAL INSTITUTION FOR COLLABORATIVE RESEARCH AND EDUCATIONHU Doc. No.151
April 1, 2014
(Purpose)
Article 1 These Regulations shall prescribe the organization and administration of the
Hokkaido University Global Institution for Collaborative Research and Education(hereinafter referred to as "the Institution for Research and Education"), based upon theRules Concerning the Organization of Hokkaido University (HU Doc. No. 31 of 2004),
Article 37(4).
(Objectives)
Article 2 The objectives of the Institution for Research and Education shall be to invite
teaching staff from Japan and overseas with world-class education and research results, topromote international collaborative research and international collaborative education(hereinafter referred to as "international collaborative research and education") that
capitalizes upon the distinctive characteristics of Hokkaido University (hereinafter referred
to as the "University"), and to provide support for international collaborative research being
furthered independently by faculties or schools.
(Employees)
Article 3 A Director and other necessary teaching staff shall be placed in the Institution for
Research and Education.
(The Director)
Article 4 The President shall be appointed as the Director of the Institution for Researchand Education.
2. The Director shall supervise the work of the Institution for Research and Education.
(The assistant director)
Article 5 An assistant director shall be placed in the Institution for Research and Education.
2. A vice president designated by the President shall be appointed as the assistant director.
3. The assistant director shall assist the Director in his or her duties and shall take over those duties in the event of the latter being incapacitated.
(Global stations)
Article 6 The following global stations shall be placed in the Institution for Research and
Education to promote international collaborative research and education that capitalizes
upon the distinctive characteristics of the University.
(1) The Global Station for Quantum Medical Science and Engineering(2) The Global Station for Zoonosis Control(3) The Global Station for Food, Land and Water Resources(4) The Global Station for Soft Matter(5) The Global Station for Big Data and Cybersecurity(6) The Global Station for Arctic Research
2. Full-time teaching staff from the University (including specially appointed academic staff
who come under each item of Article 3 of the Hokkaido University Specially Appointed
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Academic Staff Regulations (HU Doc. No. 35 of 2006). The same applies to Article 7(2)below.) and teaching staff invited from Japan and overseas shall be placed in the Institution
for Research and Education.
3. The period for which a global station is established shall be five years. However, thisperiod can be extended within five years if the steering committee provided for in Article 8
deems it necessary.
(Global station leaders)
Article 7 A global station leader shall be placed in each of the global stations referred to in
the items of Article 6(1).
2. The global station leader shall be one of the teaching staff of the said global station who
has been designated by the Director.
3. The global station leader shall supervise the work of the said global station under the ordersof the Director.
4. The term of office of the global station leaders shall be three years or less, and they can bereappointed.
(Steering Committee)
Article 8 A steering committee shall be placed in the Institution for Research and Education
to deliberate important matters concerning the said institution.
2. The organization and administration of the steering committee shall be prescribed
separately.
(Administration)
Article 9 The administrative work of the Institution for Research and Education shall beprocessed in the Division of International Planning, the International Affairs Department.
(Miscellaneous provisions)
Article 10 In addition to what is prescribed in these Regulations, necessary mattersregarding the operation of the Institution for Research and Education shall be prescribed
separately by the President after approval by the steering committee.
Supplementary Provisions
These Regulations come into force on April 1, 2014.
Supplementary Provisions
These Regulations come into force on April 1, 2015.
Supplementary Provisions
These Regulations come into force on April 1, 2016.
Supplementary Provisions
These Regulations come into force on July 1, 2018.

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REGULATIONS FOR THE GLOBAL INSTITUTIONFOR COLLABORATIVE RESEARCH AND EDUCATION STEERING COMMITTEE
HU Doc. No. 152
April 1, 2014
(Purpose)
Article 1 These regulations shall provide for the necessary matters concerning theorganization and administration of the Global Institution for Collaborative Research and
Education Steering Committee (hereinafter referred to as "the committee"), based upon
Article 8(2) of the Regulations for the Global Institution for Collaborative Research and
Education (HU Doc. No. 151 of 2014, "Regulations for the Institution for Education andResearch" in Article 3).
(Topics for Deliberation)
Article 2 The committee shall deliberate on the issues set forth in item (6) through item (10)of Article 2 of the National University Corporation Hokkaido University Agenda for
Hearing with Faculty Council Rules (HU Doc. No. 42 of 2015, referred to as “Hearing
Rules” in the following paragraph) and deliver opinions to the President.
2. In addition to the matters specified in the preceding paragraph, the committee shalldeliberate the following matters pertaining to the Hokkaido University Global Institution
for Collaborative Research and Education (hereinafter referred to as "the Institution for
Research and Education" in (5) below).
(1) Matters regarding personnel affairs of the faculty (excluding matters set forth in item (6)through item (10) of Article 2 of the Hearing Rules).
(2) Matters regarding the establishment, reform or termination of global stations.
(3) Matters regarding the evaluation of the educational and research activities of global
stations.
(4) Matters regarding budgets.
(5) Other important matters pertaining to the administration of the Institution for Researchand Education.
(Structure)
Article 3 The committee shall consist of the following members:(1) The director of the Global Institution for Collaborative Research and Education(referred to as "the director" in Article 5)(2) The assistant director of the Global Institution for Collaborative Research and Education(referred to as "the assistant director" in Article 5)(3) One vice president designated by the President (excluding the person mentioned in theprevious item)(4) One dean or director from each of the following categories (a-d), each of whom shall be
designated by the Presidenta) The Graduate School of Letters, the Graduate School of Law, the Faculty of
Education, the Research Faculty of Media and Communication, the Faculty of
Economics and Business, the Faculty of Public Policy

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b) The Graduate School of Information Science and Technology, the Faculty of Fisheries
Sciences, the Faculty of Environmental Earth Science, the Faculty of Science, theResearch Faculty of Agriculture, the Faculty of Advanced Life Science, the Faculty ofEngineering, the Faculty of Veterinary Medicinec) The Faculty of Pharmaceutical Sciences, the Faculty of Health Sciences, the Faculty of
Medicine, the Faculty of Dental Medicine, Hokkaido University Hospitald) Each affiliated research institute, each research center, the Field Science Center for
Northern Biosphere(5) Each global station leader as prescribed in Article 7 of the Regulations for the Institution
for Education and Research(6) Other persons whom the President deems appropriate
2. The President shall appoint the committee members mentioned in the preceding item (6)(Term of Office)
Article 4 The terms of office of the committee members indicated in paragraph 1(4) andparagraph 1(6) of the previous article shall be two years. However, the term of office of
substitute committee members shall be the remaining term of office of the previous
committee member.
2. The committee members indicated in the preceding paragraph may be reappointed.
(Committee Chair)
Article 5 The director shall be appointed as the committee chair.
2. The committee chair shall call committee meetings and preside over the said meetings.
3. The assistant director shall take over the director's duties in the event of the latter being
incapacitated.
(Proceedings)
Article 6 The committee cannot validly convene unless at least two-thirds of the committee
members are present.
2 Committee proceedings, other than those prescribed separately, shall be decided by the
majority vote of the attending committee members.
(Attendance of Persons Other Than Committee Members)
Article 7 In cases deemed necessary by the committee, persons other than committee
members may be permitted to attend committee meetings, and explanations or opinions of
the said persons may be heard.
(Committees on Special Issues)
Article 8 Committees on special issues may be established within the committee whennecessary in order to deliberate specialized matters.
(General Affairs)
Article 9 The administrative affairs of the committee shall be processed in the Division ofInternational Planning, the International Affairs Department.
(Miscellaneous Provisions)
Article 10 In addition to what is prescribed in these regulations, necessary mattersregarding the operation of the committee shall be prescribed by the said committee.

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Supplementary Provisions
These regulations come into force on April 1, 2014.
Supplementary Provisions (HU Doc. No. 196 of April 1, 2015)
These regulations come into force on April 1, 2015.
Supplementary Provisions (HU Doc. No. 191 of October 1, 2016)
These regulations come into force on October 1, 2016.
Supplementary Provisions (HU Doc. No. 163 of April 1, 2017)
1. These regulations come into force on April 1, 2017.
2. The dean of the Graduate School of Dental Medicine who was specified as a committee
member in c) of paragraph 1(4) of Article 3 prior to the revision (hereinafter referred to as“the former committee member” in this paragraph) shall be deemed to have been
appointed as a committee member under the revised regulations in c) of paragraph 1(4) of
Article 3 on the enforcement date of these regulations. The term of office of the said
member shall be the remaining term of office of the former committee member on theenforcement date, notwithstanding the revised provisions of Article 4(1).
Supplementary Provisions (HU Doc. No. 182 of June 20, 2017)
These regulations come into force on June 20, 2017 and apply retroactively from April 1,
2017.
Supplementary Provisions (HU Doc. No. 98 of July 1, 2018)
These regulations come into force on July 1, 2018.

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Final Evaluation Report | Global Station for Zoonosis Control, GI-CoRE, Hokkaido University

Final Evaluation Report

外部評価報告書

Published by:

発

Global Institution for Collaborative Research

国際連携研究教育局（GI-CoRE）

July 2020

行：

Global Station for Zoonosis Control,

北海道大学

and Education (GI-CoRE),

人獣共通感染症グローバルステーション

Website: https://gi-core.oia.hokudai.ac.jp/gsz/

ウェブサイト : https://gi-core.oia.hokudai.ac.jp/gsz/

Hokkaido University

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