Inter-regional study of transmission, adaptation and pathogenesis of viruses with pandemic potential in Southeast Asia and West/Central Africa

项目摘要/摘要 我们将在东南亚和中西建立新发传染病研究中心 非洲采用洲际统一保健办法，旨在提高快速反应能力 并有效地应对疫情。我们的建议建立在现有的实验室/流行病学家网络的基础上 与国家医疗保健系统密切联系。我们将确定影响涌现的因素，并 在病毒、病媒和水库一级传播，在疑似溢出条件下导致流行。 我们将重点关注在非洲具有流行潜力的高优先级RNA病毒(裂谷热病毒(RVFV)， 克里米亚刚果出血热病毒(CCHFV)和东南亚的登革病毒(DENV)也是如此 从症状监测或昆虫采样中鉴定出的病毒(X病)。我们要攻坚克难 在新出现的传染病方面通过以下具体目标：1)加强监测和发现 未知的有可能传染给人类的RNA病毒。我们将实行自治 太阳能移动行李箱实验室，用于现场快速鉴定病原体。连接到 云计算系统将促进医疗中心和实验室之间的数据分析和共享。 我们将调查不同生态环境下昆虫体内存在的病原体。我们将开发新的诊断方法 这些病毒的工具，并在人群中进行流行率和行为研究，以确定 风险因素。2)了解高危地方性RNA病毒的传播动态 疫情爆发。我们将重点关注塞内加尔和喀麦隆的RVFV和CCHFV，以及柬埔寨的DENV。我们会 在动物和人类中使用更具特异性的多重分析方法进行调查。我们的目标是获得更好的 关于流行率、传播动力学和识别主要昆虫媒介和动物的知识 水库。3)了解影响RNA病毒适应新宿主的因素。我们将使用 使用相关细胞生成和研究关键候选病毒突变的最先进技术 包括人类在内的物种。我们将研究这些病毒对不同品系昆虫的感染效果 估计传播风险。这一目标将有助于更好地理解这些病毒对 新的主机，并将有助于设计更多的检测方法。4)宿主适应性免疫研究 应对东南亚和非洲新出现的传染病。我们将增加我们的洞察力 单细胞水平的获得性免疫反应和人类的序列-功能关系 在传染病(DENV、RVFV、CCHFV)过程中产生的抗体 单细胞水平的抗体库分析。我们将研究功能和表征结构在一个 单抗水平。我们将对细胞免疫在DENV疾病中的作用提供新的理解。 拟议的活动将允许实施基础设施和疫情分析管道。 在具有潜在大流行威胁的病毒传播地区做好准备。

Project Summary/Abstract We will establish an Emerging Infectious Disease Research Center in Southeast Asia and West/Central Africa with an inter-continental one health approach designed to improve the capacity to respond rapidly and effectively to outbreaks. Our proposal is built on an existing network of laboratories/epidemiologists in close contact with national healthcare systems. We will identify factors influencing emergence and transmission at the virus, vector and reservoir level, leading to epidemics in suspected spillover conditions. We will focus on high priority RNA viruses with epidemic potential in Africa (Rift Valley Fever virus (RVFV), Crimean Congo Hemorrhagic Fever Virus (CCHFV)) and in Southeast Asia (dengue virus (DENV)) as well as viruses (Disease X) identified from symptomatic surveillance or insect sampling. We will tackle problems in emerging infectious diseases by the following specific aims: 1) Enhance surveillance and detect unknown RNA viruses with potential for spillover to humans. We will implement an autonomous solar-powered mobile suitcase laboratory for rapid pathogen identification in the field. Connection to a cloud computing system will facilitate data analysis and sharing among healthcare centers and laboratories. We will survey pathogens present in insects in different ecological settings. We will develop new diagnostic tools for these viruses and conduct prevalence and behavioral studies in human populations to determine risk factors. 2) Understand transmission dynamics of endemic RNA viruses with high risk of outbreak. We will focus on RVFV and CCHFV in Senegal and Cameroun, and DENV in Cambodia. We will perform surveys in animals and humans using a more specific multiplex assay. We aim at obtaining better knowledge on prevalence, transmission dynamics, and identifying major insect vectors and animal reservoirs. 3) Understand factors influencing adaptation of RNA viruses to new hosts. We will use state of the art technology to generate and study key candidate viral mutations using cells from relevant species including humans. We will study efficacy of these viruses in infection of various strains of insects to estimate transmission risks. This aim will lead to better understanding of the adaptation of these viruses to new hosts and will help design more detection methods. Lastly, 4) Study of host adaptive immune responses to emerging infectious diseases in South-East Asia and Africa. We will increase our insight into the adaptive immune response at a single cell level and the sequence-function relationship of human antibodies generated during infectious diseases (DENV, RVFV, CCHFV) by combining sequencing at a single cell level with antibody repertoire analysis. We will study function and characterize structure at a single antibody level. We will provide novel understanding of the role of cellular immunity in DENV disease. The proposed activity will allow the implementation of infrastructure and an analysis pipeline for outbreak preparedness in areas where viruses with potential pandemic threats circulate.