RAPID: Tackling Critical Issues in the Ebola Epidemic through Modeling: Viral Evolution

目前尚不清楚埃博拉病毒的进化是否会导致传染性的变化。在2014年西非埃博拉疫情期间，有证据表明，该病毒的遗传变化率、替代率高于以往疫情。研究人员将研究基因进化如何使病毒的传染性增强或减弱，它将如何帮助或阻碍人类对埃博拉病毒感染的免疫反应，以及病毒进化将如何影响现有和未来的治疗方法。埃博拉基因组上的目标区域编码一种糖蛋白，这种糖蛋白位于病毒和受感染细胞的表面。它是中和抗体的重要靶点，其功能和形态的改变会影响抗体的识别。研究人员将从埃博拉病毒的近期和历史演变中确定其功能含义，并对所有可能中断糖蛋白与抗体结合但不会显著降低折叠稳定性的突变进行建模。这项研究将为卫生机构提供潜在埃博拉病毒突变的基本“观察名单”，并相应预测这些突变将如何影响疾病进程。

Whether evolution of the Ebola virus will lead to changes in infectivity is currently unknown. During the 2014 Ebola epidemic in West Africa, evidence suggests that the virus has had a higher rate of genetic change, substitution rate, than in prior outbreaks. The investigators will study how genetic evolution may make the virus more or less infectious, how it will either help or hinder the human immune response to Ebola virus infections, and how viral evolution will impact existing and future therapies. The region of interest on the Ebola genome encodes for a glycoprotein that is located on the surface of the virus and infected cells. It is an important target for neutralizing antibodies and changes in its function and morphology could impact antibody recognition. The investigators will determine the functional implications from the recent and historic evolution of the Ebola virus, as well as model all possible mutations that could interrupt binding between the glycoprotein and antibodies but that would not significantly reduce folding stability. This research will provide health agencies an essential "watch list" of potential Ebola virus mutations with corresponding predictions of how these mutations are expected to impact the disease process.