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

RAPID：通过建模解决埃博拉疫情中的关键问题：病毒进化

• 批准号: 1521049
• 负责人: Frederick Ytreberg
• 金额: $ 7.22万
• 依托单位: Regents of the University of Idaho
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1521049&HistoricalAwards=false
• 关键词: RAPID; Tackling; Critical; Issues; Ebola

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.

埃博拉病毒的进化是否会导致传染性的变化目前尚不清楚。在2014年西非埃博拉疫情期间，有证据表明，该病毒的基因变化率，即替代率，比以前的疫情更高。研究人员将研究遗传进化如何使病毒更具或更少感染性，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。埃博拉病毒基因组上的感兴趣区域编码位于病毒和感染细胞表面的糖蛋白。 它是中和抗体的重要靶标，其功能和形态的变化可能影响抗体识别。研究人员将确定埃博拉病毒最近和历史演变的功能影响，并对所有可能中断糖蛋白和抗体之间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一份潜在埃博拉病毒突变的重要“观察名单”，并相应预测这些突变预计将如何影响疾病进程。