bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained Specific and Cross-Reactive T Cell Responses to Zika and Dengue Virus NS3 in West Africa
Authors: Herrera Bobby Brooke , Tsai Wen-Yang , Chang Charlotte A. , Hamel Donald J. , Wang Wei-Kung , Lu Yichen , Mboup Souleymane , Kanki Phyllis J. 
Published: January 2018

ABSTRACT
Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown that T cell responses to Asian ZIKV infection are important for protection, and that previous dengue virus (DENV) exposure amplifies the protective T cell response to Asian ZIKV. Human T cell responses to African ZIKV infection, however, remain unexplored. Here, we utilized the modified anthrax toxin delivery system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay. Using human ZIKV and DENV samples from Senegal, West Africa, our results demonstrate specific and cross-reactive T cell responses to nonstructural protein 3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential sample analyses revealed immune responses sustained many years after infection. These results have important implications for African ZIKV/DENV vaccine development, as well as for potential flavivirus diagnostics based on T cell responses.

IMPORTANCE
The recent Zika virus (ZIKV) epidemic in Latin America and the associated congenital microcephaly and Guillain-Barré syndrome have raised questions as to why we have not recognized these distinct clinical diseases in Africa. The human immunologic response to ZIKV and related flaviviruses in Africa represents a research gap that may shed light on the mechanisms contributing to protection. The goal of our study was to develop an inexpensive assay to detect and characterize the T cell response to African ZIKV and DENV. Our data show long-term specific and cross-reactive human immune responses against African ZIKV and DENV, suggesting the usefulness of a diagnostic based on the T cell response. Additionally, we show that prior flavivirus exposure influences the magnitude of the T cell response. The identification of immune responses to African ZIKV and DENV is of relevance to vaccine development.
Specific Mutations in the PB2 Protein of Influenza A Virus Compensate for the Lack of Efficient Interferon Antagonism of the NS1 Protein of Bat Influenza A-Like Viruses
Authors: Aydillo Teresa , Ayllon Juan , Pavlisin Amzie , Martinez-Romero Carles , Tripathi Shashank , Mena Ignacio , Moreira-Soto Andrés , Vicente-Santos Amanda , Corrales-Aguilar Eugenia , Schwemmle Martin , García-Sastre Adolfo 
Published: January 2018

ABSTRACT

Recently, two new influenza A-like viruses have been discovered in bats, A/little yellow-shouldered bat/Guatemala/060/2010 (HL17NL10) and A/flat-faced bat/Peru/033/2010 (HL18NL11). The hemagglutinin (HA)-like (HL) and neuraminidase (NA)-like (NL) proteins of these viruses lack hemagglutination and neuraminidase activities, despite their sequence and structural homologies with the HA and NA proteins of conventional influenza A viruses. We have now investigated whether the NS1 proteins of the HL17NL10 and HL18NL11 viruses can functionally replace the NS1 protein of a conventional influenza A virus. For this purpose, we generated recombinant influenza A/Puerto Rico/8/1934 (PR8) H1N1 viruses containing the NS1 protein of the PR8 wild-type, HL17NL10, and HL18NL11 viruses. These viruses (r/NS1PR8, r/NS1HL17, and r/NS1HL18, respectively) were tested for replication in bat and nonbat mammalian cells and in mice. Our results demonstrate that the r/NS1HL17 and r/NS1HL18 viruses are attenuated
in vitro
and
in vivo
. However, the bat NS1 recombinant viruses showed a phenotype similar to that of the r/NS1PR8 virus in STAT1
−/−
human A549 cells and mice, both
in vitro
and
in vivo
systems being unable to respond to interferon (IFN). Interestingly, multiple mouse passages of the r/NS1HL17 and r/NS1HL18 viruses resulted in selection of mutant viruses containing single amino acid mutations in the viral PB2 protein. In contrast to the parental viruses, virulence and IFN antagonism were restored in the selected PB2 mutants. Our results indicate that the NS1 protein of bat influenza A-like viruses is less efficient than the NS1 protein of its conventional influenza A virus NS1 counterpart in antagonizing the IFN response and that this deficiency can be overcome by the influenza virus PB2 protein.

IMPORTANCE
Significant gaps in our understanding of the basic features of the recently discovered bat influenza A-like viruses HL17NL10 and HL18NL11 remain. The basic biology of these unique viruses displays both similarities to and differences from the basic biology of conventional influenza A viruses. Here, we show that recombinant influenza A viruses containing the NS1 protein from HL17NL10 and HL18NL11 are attenuated. This attenuation was mediated by their inability to antagonize the type I IFN response. However, this deficiency could be compensated for by single amino acid replacements in the PB2 gene. Our results unravel a functional divergence between the NS1 proteins of bat influenza A-like and conventional influenza A viruses and demonstrate an interplay between the viral PB2 and NS1 proteins to antagonize IFN.
HIV-1 Vif's Capacity To Manipulate the Cell Cycle Is Species Specific
Authors: Evans Edward L. , Becker Jordan T. , Fricke Stephanie L. , Patel Kishan , Sherer Nathan M. 
Published: January 2018

ABSTRACT

Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production, reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors cyclin T1 (CCNT1) and exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's postintegration stages, we studied HIV-1
NL4-3
gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1-compatible versions of CCNT1 and XPO1 (3T3.CX cells). 3T3.CX cells supported both Rev-independent and Rev-dependent viral gene expression and produced relatively robust levels of virus particles, confirming that CCNT1 and XPO1 represent the predominant blocks to these stages. Unexpectedly, however, 3T3.CX cells were remarkably resistant to virus-induced cytopathic effects observed in human cell lines, which we mapped to the viral protein Vif and its apparent species-specific capacity to induce G
2
/M cell cycle arrest. Vif was able to mediate rapid degradation of human APOBEC3G and the PPP2R5D regulatory B56 subunit of the PP2A phosphatase holoenzyme in mouse cells, thus demonstrating that Vif
NL4-3
's modulation of the cell cycle can be functionally uncoupled from some of its other defined roles in CUL5-dependent protein degradation. Vif was also unable to induce G
2
/M cell cycle arrest in other nonhuman cell types, including cells derived from nonhuman primates, leading us to propose that one or more human-specific cofactors underpin Vif's ability to modulate the cell cycle.

IMPORTANCE
Cells derived from mice and other rodents exhibit profound blocks to HIV-1 replication, thus hindering the development of a low-cost small-animal model for studying HIV/AIDS. Here, we engineered otherwise-nonpermissive mouse cells to express HIV-1-compatible versions of two species-specific host dependency factors, cyclin T1 (CCNT1) and exportin-1 (XPO1) (3T3.CX cells). We show that 3T3.CX cells rescue HIV-1 particle production but, unexpectedly, are completely resistant to virus-induced cytopathic effects. We mapped these effects to the viral accessory protein Vif, which induces a prolonged G
2
/M cell cycle arrest followed by apoptosis in human cells. Combined, our results indicate that one or more additional human-specific cofactors govern HIV-1's capacity to modulate the cell cycle, with potential relevance to viral pathogenesis in people and existing animal models.
Kaposi's Sarcoma-Associated Herpesvirus K8 Is an RNA Binding Protein That Regulates Viral DNA Replication in Coordination with a Noncoding RNA
Authors: Liu Dongcheng , Wang Yan , Yuan Yan 
Published: January 2018

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication and constant primary infection of fresh cells are crucial for viral tumorigenicity. The virus-encoded bZIP family protein K8 plays an important role in viral DNA replication in both viral reactivation and
de novo
infection. The mechanism underlying the functional role of K8 in the viral life cycle is elusive. Here, we report that K8 is an RNA binding protein that also associates with many other proteins, including other RNA binding proteins. Many protein-protein interactions involving K8 are mediated by RNA. Using a UV
c
ross
-l
inking and
i
mmuno
p
recipitation (CLIP) procedure combined with high-throughput sequencing, RNAs that are associated with K8 in BCBL-1 cells were identified, including both viral (PAN, T1.4, T0.7, etc.) and cellular (MALAT-1, MRP, 7SK, etc.) RNAs. An RNA binding motif in K8 was defined, and mutation of the motif abolished the ability of K8 to bind to many noncoding RNAs, as well as viral DNA replication during
de novo
infection, suggesting that the K8 functions in viral replication are carried out through RNA association. The functions of K8 and associated T1.4 RNA were investigated in detail, and the results showed that T1.4 mediates the binding of K8 to ori-Lyt DNA. The T1.4-K8 complex physically bound to KSHV ori-Lyt DNA and recruited other proteins and cofactors to assemble a replication complex. Depletion of T1.4 abolished DNA replication in primary infection. These findings provide mechanistic insights into the role of K8 in coordination with T1.4 RNA in regulating KSHV DNA replication during
de novo
infection.

IMPORTANCE
Genomewide analyses of the mammalian transcriptome revealed that a large proportion of sequence previously annotated as noncoding regions is actually transcribed and gives rise to stable RNAs. The emergence of a large number of noncoding RNAs suggests that functional RNA-protein complexes, e.g., ribosomes or spliceosomes, are not ancient relics of the last ribo-organism but would be well adapted to a regulatory role in biology. K8 has been puzzling because of its unique characteristics, such as multiple regulatory roles in gene expression and DNA replication without DNA binding capability. This study reveals the mechanism underlying its regulatory role by demonstrating that K8 is an RNA binding protein that binds to DNA and initiates DNA replication in coordination with a noncoding RNA. It is suggested that many K8 functions, if not all, are carried out through its associated RNAs.
Two-year outcomes of intravitreal ziv-aflibercept
Authors: Mansour Ahmad M , Ashraf Mohammed , Charbaji Abdulrazzak , Younis Muhammad H , Souka Ahmed A , Dogra Avantika , Mansour Hana A , Chhablani Jay 
Published: January 2018

AimTo assess the two-year outcome of intravitreal ziv-aflibercept (IVZ) in eyes with macular diseases.MethodsConsecutive subjects with various macular diseases that received six or more of 0.05 mL IVZ (1.25 mg) injections with at least 1 year follow-up were included. Outcome measures were best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution) and central macular thickness (CMT) on spectral domain optical coherence tomography. Paired comparison was done using Wilcoxon signed-rank test calculator.Results107 eyes of 91 subjects received IVZ and were followed with mean±SD follow-up interval of 1.48±0.44 months following treat and extend or pro-re-nata protocol. The distribution included neovascular macular degeneration (42 eyes), diabetic macular oedema (32 eyes) and macular oedema secondary to retinal vein occlusion (11 eyes). Fifty eyes were naive, while 57 eyes were previously treated. Combining all disease categories, CMT decreased significantly by 133.0±153.0 µm at the 24-month follow-up (P<0.001) with BCVA gain of 0.35±0.37 at the 24-month follow-up (P<0.001) with mean number of injections of 8.5 at month 12, 2.4 between 12 and 18 month and 1.7 between 18 and 24 month. Ocular and systemic adverse effects included one episode of transient uveitis and one instance of central retinal artery occlusion after 1121 injections.ConclusionsIVZ appears safe and efficacious in the therapy of macular diseases through 2 years.
Current strategies and successes in engaging women in vector control: a systematic review
Authors: Gunn Jayleen K L , Ernst Kacey C , Center Katherine E , Bischoff Kristi , Nuñez Annabelle V , Huynh Megan , Okello Amanda , Hayden Mary H 
Published: January 2018

IntroductionVector-borne diseases (VBDs) cause significant mortality and morbidity in low-income and middle-income countries and present a risk to high-income countries. Vector control programmes may confront social and cultural norms that impede their execution. Anecdotal evidence suggests that incorporating women in the design, delivery and adoption of health interventions increases acceptance and compliance. A better understanding of programmes that have attempted to increase women’s involvement in vector control could help shape best practices. The objective of this systematic review was to assess and critically summarise evidence regarding the effectiveness of women participating in vector control.MethodsSeven databases were searched from inception to 21 December 2015. Two investigators independently reviewed all titles and abstracts for relevant articles. Grey literature was searched by assessing websites that focus on international development and vector control.ResultsIn total, 23 articles representing 17 unique studies were included in this review. Studies discussed the involvement of women in the control of vectors for malaria (n=10), dengue (n=8), human African trypanosomiasis (n=3), schistosomiasis (n=1) and a combination (malaria and schistosomiasis, n=1). Seven programmes were found in the grey literature or through personal communications. Available literature indicates that women can be successfully engaged in vector control programmes and, when given the opportunity, they can create and sustain businesses that aim to decrease the burden of VBDs in their communities.ConclusionThis systematic review demonstrated that women can be successfully engaged in vector control programmes at the community level. However, rigorous comparative effectiveness studies need to be conducted.
Making sense of child, early and forced marriage among Syrian refugee girls: a mixed methods study in Lebanon
Authors: Bartels Susan Andrea , Michael Saja , Roupetz Sophie , Garbern Stephanie , Kilzar Lama , Bergquist Harveen , Bakhache Nour , Davison Colleen , Bunting Annie 
Published: January 2018

IntroductionThe Syrian conflict has resulted in over 2.3 million child refugees in the Middle East and the prevalence of early marriage has reportedly increased among displaced Syrian families. This study explores the underlying factors contributing to child marriage among Syrian refugees in Lebanon with the goal of informing community-based strategies to address the issue.MethodsIn July–August 2016, trained interviewers collected self-interpreted stories in Lebanon using Cognitive Edge’s SenseMaker, a mixed-method data collection tool. Participants included married and unmarried Syrian girls, Syrian parents as well as married and unmarried men. Each participant shared a story about the experiences of Syrian girls and then interpreted the story by plotting their perspectives on a variety of questions. Patterns in the responses were analysed in SPSS and the accompanying qualitative narratives were reviewed to facilitate interpretation of the quantitative results.Results1422 self-interpreted stories from 1346 unique participants were collected with 40% of shared stories focused on (n=332) or mentioning (n=245) child marriage. Quantitative data summarised the different perspectives of female and male participants. Syrian girls and mothers were more likely to share stories about protection/security and/or education and were more likely to report that girls were overprotected. Male participants were more likely to share stories about financial security as well as sexual exploitation of girls and more often reported that girls were not protected enough. Despite these gendered perspectives, many of the shared narratives highlighted similar themes of financial hardship, lack of educational opportunities and safety concerns around sexual and gender-based violence (SGBV).ConclusionsA complex myriad of factors contribute to early marriage including poverty, lack of educational opportunities and concerns about SGBV. Sexual exploitation under the guise of marriage is a reality for some Syrian girls. Gender-specific strategies to address child marriage might be more effective in reducing this harmful practice.
Examining changes in the equity of physician distribution in Japan: a specialty-specific longitudinal study
Authors: Hara Koji , Kunisawa Susumu , Sasaki Noriko , Imanaka Yuichi 
Published: January 2018

ObjectivesIn this longitudinal study, we examined changes in the geographical distribution of physicians in Japan from 2000 to 2014 by clinical specialty with adjustments for healthcare demand based on population structure.MethodsThe Japanese population was adjusted for healthcare demand using health expenditure per capita stratified by age and sex. The numbers of physicians per 100 000 demand-adjusted population (DAP) in 2000 and 2014 were calculated for subprefectural regions known as secondary medical areas. Disparities in the geographical distribution of physicians for each specialty were assessed using Gini coefficients. A subgroup analysis was conducted by dividing the regions into four groups according to urban–rural classification and initial physician supply.ResultsOver the study period, the number of physicians per 100 000 DAP decreased in all specialties assessed (internal medicine: −6.9%, surgery: −26.0%, orthopaedics: −2.1%, obstetrics/gynaecology (per female population): −17.5%) except paediatrics (+33.3%) and anaesthesiology (+21.1%). No reductions in geographical disparity were observed in any of the specialties assessed. Geographical disparity increased substantially in internal medicine, surgery and obstetrics and gynaecology(OB/GYN). Rural areas with lower initial physician supply experienced the highest decreases in physicians per 100 000 DAP for all specialties assessed except paediatrics and anaesthesiology. In contrast, urban areas with lower initial physician supply experienced the lowest decreases in physicians per 100 000 DAP in internal medicine, surgery, orthopaedics and OB/GYN, but the highest increase in anaesthesiology.ConclusionBetween 2000 and 2014, the number of physicians per 100 000 DAP in Japan decreased in all specialties assessed except paediatrics and anaesthesiology. There is also a growing urban–rural disparity in physician supply in all specialties assessed except paediatrics. Additional measures may be needed to resolve these issues and improve physician distribution in Japan.
Patients’ and therapists’ experiences with a new treatment programme for eating disorders that combines physical exercise and dietary therapy: the PED-t trial. A qualitative study protocol
Authors: Pettersen Gunn , Rosenvinge Jan H , Bakland Maria , Wynn Rolf , Mathisen Therese Fostervold , Sundgot-Borgen Jorunn 
Published: January 2018

IntroductionWomen with bulimia nervosa and binge eating disorder often suffer for many years before they seek professional help. Evidence-based treatments like cognitive–behavioural therapy (CBT) might be poorly accessible, and about 50% of those who receive CBT respond to it. Such outcome may reflect the heterogeneous nature of eating disorders, and addressing this heterogeneity calls for expanding the portfolio of treatment options. In particular, it is important to explore such options’ acceptability, tolerability and affordability expressed through experiences with the treatment. This protocol outlines the rationale and design of a qualitative study. It captures experiences from patients and therapists who were involved in a randomised controlled trial (RCT) exploring the efficacy of a new group-based treatment programme combining physical exercise and dietary therapy.Methods and analysis15 patients with bulimia nervosa or binge eating disorder, 10 therapists (physical trainers and dietitians) and 6–10 patients who dropped out of the RCT will be semistructurally interviewed. All interviews will be analysed using a systematic text condensation approach.Ethics and disseminationResults will be presented in peer-reviewed international journals, and at relevant international conferences. Key findings will be available to study participants as well as to patient organisations and health authorities. The overall study meets the intent and requirements of the Health Research Act and the Declaration of Helsinki. It is approved by the regional committee for medical research ethics (2013/1871).Trial registration numberNCT02079935; Pre-results.
Cohort profile: effect of malaria in early pregnancy on fetal growth in Benin (RECIPAL preconceptional cohort)
Authors: Accrombessi Manfred , Yovo Emmanuel , Cottrell Gilles , Agbota Gino , Gartner Agnès , Martin-Prevel Yves , Fanou-Fogny Nadia , Djossinou Diane , Zeitlin Jennifer , Tuikue-Ndam Nicaise , Bodeau-Livinec Florence , Houzé Sandrine , Jackson Nicola , Ayemonna Paul , Massougbodji Achille , Cot Michel , Fievet Nadine , Briand Valérie 
Published: January 2018

PurposeREtard de Croissance Intra-uterin et PALudisme (RECIPAL) is an original preconceptional cohort designed to assess the consequences of malaria during the first trimester of pregnancy, which is a poorly investigated period in Africa and during which malaria may be detrimental to the fetus.ParticipantsFor this purpose, a total of 1214 women of reproductive age living in Sô-Ava and Akassato districts (south Benin) were followed up monthly from June 2014 to December 2016 until 411 of them became pregnant. A large range of health determinants was collected both before and during pregnancy from the first weeks of gestation to delivery. Five Doppler ultrasound scans were performed for early dating of the pregnancy and longitudinal fetal growth assessment.Findings to datePregnant women were identified at a mean of 6.9 weeks of gestation (wg). Preliminary results confirmed the high prevalence of malaria in the first trimester of pregnancy, with more than 25.4% of women presenting at least one microscopic malarial infection during this period. Most infections occurred before six wg. The prevalence of low birth weight, small birth weight for gestational age (according to INTERGROWTH-21st charts) and preterm birth was 9.3%, 18.3% and 12.6%, respectively.Future plansREtard de Croissance Intra-uterin et PALudisme (RECIPAL) represents at this time a unique resource that will provide information on multiple infectious (including malaria), biological, nutritional and environmental determinants in relation to health outcomes in women of reproductive age, pregnant women and their newborns. It will contribute to better define future recommendations for the prevention of malaria in early pregnancy and maternal malnutrition in Africa. It confirms that it is possible to constitute a preconceptional pregnancy cohort in Africa and provides valuable information for researchers starting cohorts in the future.