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

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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.