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

项目总结/摘要 我们将在东南亚和西/中部建立一个新兴传染病研究中心 非洲采用旨在提高快速反应能力的洲际统一保健办法 有效地控制疾病的爆发。我们的建议是建立在现有的实验室/流行病学家网络， 与国家卫生系统密切联系。我们将确定影响出现的因素， 在病毒、病媒和水库一级传播，在疑似外溢条件下导致流行病。 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（登革热病毒（DENV 从症状监测或昆虫采样中鉴定出的病毒（X病）。我们会解决问题 （1）加强监察及检测新出现的传染病， 可能会传染给人类的未知RNA病毒。我们将实施一项自主的 太阳能移动的手提箱实验室，用于在实地快速鉴定病原体。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中昆虫中存在的病原体。我们将开发新的诊断 这些病毒的工具，并在人群中进行流行和行为研究，以确定 危险因素2)了解具有高风险的地方性RNA病毒的传播动态 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。我们将 使用更特异的多重测定在动物和人类中进行调查。我们的目标是获得更好的 关于流行率、传播动力学和确定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 使用来自相关组织的细胞产生和研究关键候选病毒突变的最新技术水平 包括人类在内的物种。我们将研究这些病毒感染各种昆虫的效力， 估计传播风险。这一目标将导致更好地了解这些病毒的适应性， 新的主机，并将有助于设计更多的检测方法。4）宿主适应性免疫的研究 东南亚和非洲新出现的传染病的应对措施。我们将增加我们的洞察力 单细胞水平的适应性免疫反应和人类免疫系统的序列-功能关系 在传染病（DENV，RVFV，CCHFV）期间产生的抗体， 单细胞水平抗体库分析。我们将研究功能和表征结构在一个 单抗体水平。我们将为细胞免疫在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分析管道， 在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.