Mechanisms of host resistance and viral tolerance in bats, linking phenotype to genotype

源自动物的新发传染病对人类健康和经济产生重大影响。埃博拉病毒和亨尼帕病毒是蝙蝠传播的病毒性病原体，最近跨越物种屏障，感染家畜和人类。果蝠（翼足科）被认为是埃博拉病毒和亨尼帕病毒的主要宿主。然而，使果蝠与这些致命病毒共存的免疫机制尚不清楚。在这项研究中，我将研究对埃博拉病毒和亨尼帕病毒易感性不同的蝙蝠物种的病毒耐受性的遗传基础。为此，我将使用我的东道主机构的实验数据和最先进的生物信息学来完成三个目标：1)比较两种非洲果蝠对埃博拉病毒和尼帕病毒疫苗免疫攻击的抗病毒反应，这两种果蝠作为这些蝙蝠传播病毒的宿主的作用不同；2)在对埃博拉病毒易感不同的果蝠中寻找丝状病毒受体NCP1和其他相关抗病毒基因的适应特征；3)将野生蝙蝠的亨尼帕病毒感染数据与宿主基因组数据相结合，评估蝙蝠与新发亨尼帕病毒的共同进化史。本研究结果将直接有助于我们了解宿主耐药性和病毒耐受性，从而为医学和制药应用提供基础。

Emerging infectious diseases with origin in animals have major impact on human health and economy. Ebolaviruses and henipaviruses are bat borne viral pathogens that have recently crossed the species barrier to infect domestic animals and humans. Fruit bats (Pteropodidae) are the assumed primary reservoir of ebolaviruses and henipaviruses. However, the immune mechanisms that enable fruit bats to co-exist with these deadly viruses are poorly understood. In this study I will investigate the genetic underpinnings of viral tolerance in bat species that differ in their susceptibility to ebolaviruses and henipaviruses. For this purpose I will use experimental data from my host institution and state-of-the-art bioinformatics to complete three objectives: 1) compare the antiviral response to immune challenge with Ebola virus and Nipah virus vaccines in two species of African fruit bats that differ in their roles as reservoirs of these bat-borne viruses, 2) look for signatures of adaptation in the filovirus receptor NCP1 and other related antiviral genes in fruit bats that differ in their susceptibility to ebolaviruses, 3) assess co-evolutionary history between bats and emerging henipaviruses by combining henipavirus infection data from wild bats with host genomic data. The outcomes of this study will directly contribute to our understanding of host resistance and viral tolerance, and thereby provide a basis for medical and pharmaceutical applications.