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International Research Center for Infectious Diseases

Department of Special Pathogens
高病原性感染症系
Professor
Visiting Professor
Visiting Professor
Associate Professor
Associate Professor

Kei Sato, Ph.D.
Masaki Imai, D.V.M., Ph.D.
Seiya Yamayoshi, D.V.M., Ph.D.
Takeshi Ichinohe, Ph.D.
Jumpei Ito, Ph.D., D.V.M.

教 授
客員教授
客員教授
准教授
准教授

博士（医学）
博士（獣医学）
博士（医学）
博士（工学）
博士（理学）

佐今山一伊藤井吉戸東正誠
猛潤

佳樹也
志平

The aim of this laboratory is to launch an interdisciplinary research platform tocomprehensively understand the behavior of viruses from macroscale tomicroscale. COVID pandemic alarmed the importance of understanding viraltransmissibility and spreading pathway. These knowledges are brought fromepidemiology and public health (science at macroscale). Viral surveillance,molecular phylogenetic and bioinformatics provide information of the variant
currently spreading (science at macroscale). “Science at mesoscale”, the use ofanimal models and cell cultures, performing experiments, and assessing clinicaldata, provide the knowledge of viral pathogenicity, features and drug efficacy. Whencertain variants that are resistant to antivirals or vaccines emerged, the molecularmechanisms of actions should be understood. For that, the understanding basedon structural biology is essential (science at micro scale). Our study will launch theplatform to perform multiscale investigation of viruses.

1.  Virological characteristics of the SARS-CoV-2
XBB variant derived from recombination oftwo Omicron subvariants
Tomokazu Tamura1, Jumpei Ito, Keiya Uriu, Jiri
Zahradnik2, Izumi Kida1, Yuki Anraku1, HeshamNasser3, Maya Shofa4, Yoshitaka Oda1, Spyros
Lytras5, Naganori Nao1, Yukari Itakura1, Sayaka
Deguchi6, Rigel Suzuki1, Lei Wang1, Mst Monira Begum3, Shunsuke Kita1, Hisano Yajima6, Jiei Sasaki6,Kaori Sasaki-Tabata7, Ryo Shimizu3, Masumi Tsuda1, Yusuke Kosugi, Shigeru Fujita, Lin Pan, Daniel
Sauter, Kumiko Yoshimatsu1, Saori Suzuki1, Hiroyuki Asakura8, Mami Nagashima8, Kenji Sadamasu8, Kazuhisa Yoshimura8, Yuki Yamamoto9,Tetsuharu Nagamoto9, Gideon Schreiber2, Katsumi
Maenaka1, Genotype to Phenotype Japan (G2P-Japan) Consortium, Takao Hashiguchi6, Terumasa
Ikeda3, Takasuke Fukuhara1, Akatsuki Saito4, Shin-ya Tanaka1, Keita Matsuno1, Kazuo Takayama6, Kei
Sato:1
Hokkaido University, Japan; 2Charles University,Czechia; 3Kumamoto University, Japan; 4Universityof Miyazaki, Japan; 5Medical Research Council-University of Glasgow Centre for Virus Research,UK; 6Kyoto University, Japan; 7Kyushu University,Japan; 8Tokyo Metropolitan Institute of Public
Health, Japan; 9HiLung, Inc., Japan
In late 2022, SARS-CoV-2 Omicron subvariants
have become highly diversified, and XBB is spreading
rapidly around the world. Our phylogenetic analyses
suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 andBM.1.1.1 (a progeny of BA.2.75), during the summerof 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date andis more fusogenic than BA.2.75. The recombination

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breakpoint is located in the receptor-binding domainof spike, and each region of the recombinant spike
confers immune evasion and increases fusogenicity.
We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally,
the intrinsic pathogenicity of XBB.1 in male hamsters

is comparable to or even lower than that of BA.2.75.
Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2variant to increase its fitness through recombination
rather than substitutions.

Publications
Keiya Uriu, Jumpei Ito, Jiri Zahradnik, Shigeru Fujita,
Yusuke Kosugi, Gideon Schreiber, Genotype toPhenotype Japan (G2P-Japan) Consortium, Kei
Sato. Enhanced Transmissibility, Infectivity, andImmune Resistance of the SARS-CoV-2 Omicron
XBB.1.5 Variant. Lancet Infectious Diseases
23(3):280–81 (2023).
Shiho Torii, Kwang Su Kim, Jun Koseki, Rigel Suzuki,
Shoya Iwanami, Yasuhisa Fujita, Yong Dam Jeong,Jumpei Ito, Hiroyuki Asakura, Mami Nagashima,
Kenji Sadamasu, Kazuhisa Yoshimura, Genotype toPhenotype Japan (G2P-Japan) Consortium, Kei
Sato, Yoshiharu Matsuura, Teppei Shimamura,
Shingo Iwami, Takasuke Fukuhara. Increased Flexibility of the SARS-CoV-2 RNA-Binding Site Causes Resistance to Remdesivir. PLoS Pathogens
19(3):e1011231 (2023).
Jumpei Ito, Rigel Suzuki, Keiya Uriu, Yukari Itakura,
Jiri Zahradnik, Kanako Terakado Kimura, SayakaDeguchi, Lei Wang, Spyros Lytras, Tomokazu Tamura, Izumi Kida, Hesham Nasser, Maya Shofa,
Mst Monira Begum, Masumi Tsuda, Yoshitaka Oda,
Tateki Suzuki, Jiei Sasaki, Kaori Sasaki-Tabata,
Shigeru Fujita, Kumiko Yoshimatsu, Hayato Ito,
Naganori Nao, Hiroyuki Asakura, Mami Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura, YukiYamamoto, Tetsuharu Nagamoto, Jin Kuramochi,Gideon Schreiber, Genotype to Phenotype Japan(G2P-Japan) Consortium, Akatsuki Saito, KeitaMatsuno, Kazuo Takayama, Takao Hashiguchi,Shinya Tanaka, Takasuke Fukuhara, Terumasa Ikeda, Kei Sato. Convergent Evolution of SARS-CoV-2
Omicron Subvariants Leading to the Emergence ofBQ.1.1 Variant. Nature Communications 14(1):2671(2023).
Tomokazu Tamura, Jumpei Ito, Keiya Uriu, Jiri Zahradnik, Izumi Kida, Yuki Anraku, Hesham Nasser,
Maya Shofa, Yoshitaka Oda, Spyros Lytras, Naganori Nao, Yukari Itakura, Sayaka Deguchi, RigelSuzuki, Lei Wang, Mst Monira Begum, Shunsuke
Kita, Hisano Yajima, Jiei Sasaki, Kaori Sasaki-Tabata, Ryo Shimizu, Masumi Tsuda, Yusuke Kosugi,Shigeru Fujita, Lin Pan, Daniel Sauter, Kumiko
Yoshimatsu, Saori Suzuki, Hiroyuki Asakura,
Mami Nagashima, Kenji Sadamasu, Kazuhisa
Yoshimura, Yuki Yamamoto, Tetsuharu Nagamoto,
Gideon Schreiber, Katsumi Maenaka, Genotype toPhenotype Japan (G2P-Japan) Consortium, Takao
Hashiguchi, Terumasa Ikeda, Takasuke Fukuhara,

Akatsuki Saito, Shinya Tanaka, Keita Matsuno, Kazuo Takayama, Kei Sato. Virological Characteristicsof the SARS-CoV-2 XBB Variant Derived from Recombination of Two Omicron Subvariants. NatureCommunications 14(1):2800 (2023).
Daichi Yamasoba, Keiya Uriu, Arnon Plianchaisuk,Yusuke Kosugi, Lin Pan, Jiri Zahradnik, Genotype
to Phenotype Japan (G2P-Japan) Consortium, Jumpei Ito, Kei Sato. Virological Characteristics of theSARS-CoV-2 Omicron XBB.1.16 Variant. Lancet Infectious Diseases 23(6):655–56 (2023).
Tomokazu Tamura, Daichi Yamasoba, Yoshitaka Oda,
Jumpei Ito, Tomoko Kamasaki, Naganori Nao, Rina
Hashimoto, Yoichiro Fujioka, Rigel Suzuki, LeiWang, Hayato Ito, Yukie Kashima, Izumi Kimura,
Mai Kishimoto, Masumi Tsuda, Hirofumi Sawa,Kumiko Yoshimatsu, Yuki Yamamoto, Tetsuharu
Nagamoto, Jun Kanamune, Yutaka Suzuki, Yusuke
Ohba, Genotype to Phenotype Japan (G2P-Japan)
Consortium, Isao Yokota, Keita Matsuno, Kazuo
Takayama, Shinya Tanaka, Kei Sato, Takasuke
Fukuhara. Comparative Pathogenicity of SARSCoV-2 Omicron Subvariants Including BA.1, BA.2,and BA.5. Communications Biology 6(1):772(2023).
Shigeru Fujita, Keiya Uriu, Lin Pan, Naganori Nao,
Koshiro Tabata, Mai Kishimoto, Yukari Itakura, Hirofumi Sawa, Izumi Kida, Tomokazu Tamura, Genotype to Phenotype Japan (G2P-Japan) Consortium, Takasuke Fukuhara, Jumpei Ito, Keita Matsuno,
Kei Sato. Impact of Imprinted Immunity Induced
by mRNA Vaccination in an Experimental Animal
Model. Journal of Infectious Diseases 228(8):1060–
65 (2023).
Shigeru Fujita, Yusuke Kosugi, Izumi Kimura, Kenzo
Tokunaga, Genotype to Phenotype Japan (G2P-Japan) Consortium, Jumpei Ito, Kei Sato. Determination of the Factors Responsible for the Tropism ofSARS-CoV-2-Related Bat Coronaviruses to Rhinolophus Bat ACE2. Journal of Virology e0099023(2023).
Izumi Kimura, Daichi Yamasoba, Hesham Nasser,
Hayato Ito, Jiri Zahradnik, Jiaqi Wu, Shigeru Fujita,Keiya Uriu, Jiei Sasaki, Tomokazu Tamura, RigelSuzuki, Sayaka Deguchi, Arnon Plianchaisuk, Kumiko Yoshimatsu, Yasuhiro Kazuma, Shuya Mitoma, Gideon Schreiber, Hiroyuki Asakura, Mami
Nagashima, Kenji Sadamasu, Kazuhisa Yoshimura,
Akifumi Takaori-Kondo, Genotype to Phenotype

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Japan (G2P-Japan) Consortium, Jumpei Ito, Kotaro
Shirakawa, Kazuo Takayama, Takashi Irie, Takao
Hashiguchi, So Nakagawa, Takasuke Fukuhara,Akatsuki Saito, Terumasa Ikeda, Kei Sato. Multiple
Mutations of SARS-CoV-2 Omicron BA.2 VariantOrchestrate Its Virological Characteristics. Journalof Virology e0101123 (2023).
Yu Kaku, Yusuke Kosugi, Keiya Uriu, Jumpei Ito, Alfredo A. Hinay, Jin Kuramochi, Kenji Sadamasu,Kazuhisa Yoshimura, Hiroyuki Asakura, Mami Nagashima, Genotype to Phenotype Japan (G2P-Japan) Consortium, Kei Sato. Antiviral Efficacy of theSARS-CoV-2 XBB Breakthrough Infection Sera
against Omicron Subvariants Including EG.5. Lancet Infectious Diseases 23(10):e395–96 (2023).
Hirofumi Aso, Jumpei Ito, Haruka Ozaki, Yukie
Kashima, Yutaka Suzuki, Yoshio Koyanagi, Kei
Sato. Single-Cell Transcriptome Analysis Illuminating the Characteristics of Species-Specific Innate
Immune Responses against Viral Infections. GigaScience 12:giad086 (2022).
Keiya Uriu, Jumpei Ito, Yusuke Kosugi, Yuri L. Tanaka, Yuka Mugita, Ziyi Guo, Alfredo A. Hinay, Olivia Putri, Yoonjin Kim, Ryo Shimizu, Mst MoniraBegum, Michael Jonathan, Genotype to Phenotype
Japan (G2P-Japan) Consortium, Akatsuki Saito,Terumasa Ikeda, Kei Sato. Transmissibility, Infectivity, and Immune Evasion of the SARS-CoV-2
BA.2.86 Variant. Lancet Infectious Diseases 23(11):e460–61 (2023).
Martin Müller, Alexandra Herrmann, Shigeru Fujita,Keiya Uriu, Carolin Kruth, Adam Strange, Jan E.
Kolberg, Markus Schneider, Jumpei Ito, Marcel A.
Müller, Christian Drosten, Armin Ensser, Genotypeto Phenotype Japan (G2P-Japan) Consortium, KeiSato, Daniel Sauter. ORF3c Is Expressed in SARSCoV-2-Infected Cells and Inhibits Innate Sensingby Targeting MAVS. EMBO Reports 24(12):e57137(2023).
Yusuke Kosugi, Arnon Plianchaisuk, Olivia Putri,Keiya Uriu, Yu Kaku, Alfredo A. Hinay, Luo Chen,
Jin Kuramochi, Kenji Sadamasu, Kazuhisa Yoshimura, Hiroyuki Asakura, Mami Nagashima, TheGenotype to Phenotype Japan (G2P-Japan) Consortium, Jumpei Ito, Kei Sato. Virological Characteristics of the SARS-CoV-2 Omicron HK.3 Variant Harboring the FLip Substitution. Lancet Microbe inpress (2023).
Yuuka Masuda, Hesham Nasser, Jiri Zahradnik,
Shuya Mitoma, Ryo Shimizu, Kayoko Nagata, Akifumi Takaori-Kondo, Gideon Schreiber, The Genotype to Phenotype Japan (G2P-Japan) Consortium,
Kotaro Shirakawa, Akatsuki Saito, Terumasa Ikeda,
Jumpei Ito, Kei Sato. Characterization of the evolutionary and virological aspects of mutations in thereceptor binding motif of the SARS-CoV-2 spike
protein. Frontiers in Virology in press.
Yusuke Kosugi, Yu Kaku, Alfredo A. Hinay, Ziyi
Guo, Keiya Uriu, Minoru Kihara, Fumitake Saito,
Yoshifumi Uwamino, Jin Kuramochi, Kotaro Shirakawa, Akifumi Takaori-Kondo, The Genotype toPhenotype Japan (G2P-Japan) Consortium, Kei
Sato. Antiviral Humoral Immunity against SARSCoV-2 Omicron Subvariants Induced by XBB.1.5
Monovalent Vaccine in Infection-Naïve and XBB-Infected Individuals. Lancet Infectious Diseases inpress (2023).
Yu Kaku, Kaho Okumura, Miguel Padilla-Blanco,
Yusuke Kosugi, Keiya Uriu, Alfredo A. Hinay, LuoChen, Arnon Plianchaisuk, Kouji Kobiyama, Ken J.
Ishii, The Genotype to Phenotype Japan (G2P-Japan) Consortium, Jiri Zahradnik, Jumpei Ito, Kei
Sato. Virological Characteristics of the SARS-CoV-2JN.1 Variant. Lancet Infectious Diseases in press(2023).