World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)

摘要 正如2019冠状病毒病、寨卡病毒、黄热病和基孔肯雅病毒大流行所强调的那样， 病毒对人类健康的威胁越来越大，但它们的出现机制仍然很差 大多数人都没有得到有效的干预措施。对其发病机理、生态学、 进化、流行病学、出现机制、诊断、疫苗和治疗仍然是关键的公共 健康需求。世界新发病毒和虫媒病毒参考中心（WRCEVA）由一个 全面、多样地收集了21个科的8,000多个病毒株，以及抗血清，抗原， cDNA克隆和其他试剂，使世界各地的研究。新增约400种病毒株 每年运送1000个病毒和试剂。WRCEVA还拥有广泛的专业知识 在新的和传统的方法来病毒鉴定和表征，并提供了关键的 支持紧急疫情应对，例如快速生成和分发关键的 COVID和Zika试剂。该提案旨在继续这些WRCEVA活动，以支持NIH资助的项目 和其他关于全球新出现病毒的研究，通过五个具体目标： 1.维护一套全面的新兴病毒、虫媒病毒和相关试剂，以支持 研究和监视。病毒收集以及抗原、抗体、cDNA克隆和其他 试剂将不断改进，以利用新出现的趋势和技术。重点 在头两年，将致力于开发冠状病毒研究的关键试剂。 2.发现、分离和鉴定新获得的病毒，以确定关系和分类 分配，并评估体外和体内宿主范围。临床和现场样本以及病毒 将接收分离株进行鉴定和表征，并添加到储存库中。关键 新发现的病毒和菌株的表型将通过使用体外和体内感染来评估。 3.对选定的病毒组进行测序和系统发育分析，以确定进化 历史和出现机制，传播/感染模式，并迅速确定 新的爆发源。关键病毒株将进行基因组测序，以生成数据库， 可用于快速确定新的爆发源，包括潜在的生物恐怖主义。 4.确定为什么黄热病病毒没有在南美洲造成大规模的城市流行， 几十年来，甚至在亚洲。我们独特的病毒株收集和虫媒病毒学专业知识将用于 研究与埃及伊蚊在城市传播的局限性有关的假设。 5.培训科学家识别和描述新出现的病毒。加强研究 在美国和世界范围内进行监测，这是限制新疫情传播的最有效方法， 将向来访的科学家提供病毒鉴定、特征描述和诊断方面的信息。

ABSTRACT As underscored by pandemic COVID-19, Zika, yellow fever and chikungunya viruses, new and emerging viruses represent increasing threats to human health, yet their mechanisms of emergence remain poorly understood, and effective interventions are not available for most. Research on their pathogenesis, ecology, evolution, epidemiology, emergence mechanisms, diagnostics, vaccines and therapeutics remain critical public health needs. The World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) comprises a comprehensive, diverse collection of over 8,000 virus strains in 21 families, as well as antisera, antigens, cDNA clones and other reagents to enable research worldwide. Approximately 400 new virus strains are added annually, and 1000 viruses and reagents are shipped annually. The WRCEVA also maintains broad expertise in both novel and traditional approaches to virus identification and characterization, and provides critical support for emergency outbreak responses as exemplified by the rapid generation and distribution of critical COVID and Zika reagents. This proposal seeks to continue these WRCEVA activities in support of NIH-funded and other research on emerging viruses worldwide, through five Specific Aims: 1. Maintain a comprehensive set of emerging viruses, arboviruses and associated reagents to support research and surveillance. The virus collection as well as antigens, antibodies, cDNA clones and other reagents will be continually enhanced to capitalize on new emergence trends and technologies. Emphasis during the first two years will be placed on the development of critical reagents for coronavirus research. 2. Discover, isolate and characterize newly acquired viruses to determine relationships and taxonomic assignments, and to assess in vitro and in vivo host range. Clinical and field samples as well as viral isolates will be received for identification and characterization, and added to the repository. Critical phenotypes of newly discovered viruses and strains will be assessed by using in vitro and in vivo infections. 3. Perform sequencing and phylogenetic analyses of selected virus groups to determine evolutionary histories and emergence mechanisms, patterns of spread/infection, and to rapidly determine the sources of new outbreaks. Key virus strains will undergo genomic sequencing to generate databases that can be exploited for the rapid determination of new outbreak sources, including potential bioterrorism. 4. Determine why yellow fever virus has not caused major urban epidemics in South America for many decades, or ever in Asia. Our unique collection of virus strains and arbovirology expertise will be used to examine hypotheses related to limitations on urban transmission by Aedes aegypti mosquitoes. 5. Train scientists in the identification and characterization of emerging viruses. To enhance research and surveillance in the U.S. and worldwide, the most efficient way to limit spread of new outbreaks, training in virus identification, characterization, and diagnostics will be provided to visiting scientists.