Biology, Evolution and Pathogenesis of Influenza A Virus

甲型流感病毒的生物学、进化和发病机制

• 批准号: 9566662
• 负责人: JACK R BENNINK
• 金额: $ 68.02万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9566662
• 关键词: Acute; Biology; Disease Outbreaks; Economics; Evolution; Goals; Host Defense Mechanism; Immunity; Influenza A virus; Kinetics; Memory; Molecular; Morbidity - disease rate; Mutation; Pathogenesis; Role; Vaccinated; Vaccination; Viral; Viral Genome; Viral Pathogenesis; Viral Proteins; Virus; Virus Diseases; War; adaptive immune response; combat; improved; influenzavirus; mortality; next generation sequencing; novel; pandemic disease; pathogen; response; vaccination strategy; vaccine efficacy; viral transmission; virus pathogenesis

Influenza A viruses (IAVs) cause seasonal outbreaks and occasional severe pandemics that are a significant burden in morbidity, mortality, and economic loss. The continuous evolution of IAV through mutation and reassortment provide molecular mechanisms to allow IAV to evade host immunity. However, there remain significant gaps in our understanding of the tug of war between host and virus, particularly, the molecular mechanisms influenza virus employs through evolution in response to host defense mechanisms and the implications this may have for vaccination strategies. By focusing on the biology, evolution and pathogenesis of the virus, first, we aim to determine the significance and extent of IAV evolution caused by acute primary and memory (vaccination) adaptive immune responses. Specifically, we will utilize next generation sequencing of the full virus genome to determine the kinetics and extent of virus evolution. We will determine whether our current vaccination strategies result in enhanced virus evolution and further whether viral evolution rate could be used as an early indicator of vaccine efficacy. Second, we want to focus on the role of influenza virus protein evolution in viral pathogenesis and transmission. Through these studies, we aim to further our understanding of IAV evolution and the underlying causative host mechanisms. It is hoped that with a better understanding of the highly adaptive IAV, these studies will uncover novel and improved ways to vaccinate and combat IAV infection.

流感病毒（IAV）引起季节性暴发和偶尔出现严重的大流行，这对发病率，死亡率和经济损失产生了重大负担。 IAV通过突变和重新分层的连续演变提供了分子机制，使IAV逃避了宿主的免疫力。 但是，我们对宿主和病毒之间的拔河战争的理解仍然存在很大的差距，尤其是，流感病毒通过进化来响应宿主防御机制采用的分子机制，以及这对疫苗接种策略的影响。 首先，通过关注病毒的生物学，进化和发病机理，我们旨在确定由急性原发性和记忆（疫苗接种）适应性免疫反应引起的IAV进化的显着性和程度。 具体而言，我们将利用完整病毒基因组的下一代测序来确定病毒进化的动力学和程度。我们将确定我们当前的疫苗接种策略是否导致病毒进化增强，并进一步将病毒进化率用作疫苗疗效的早期指标。 其次，我们要关注流感病毒蛋白进化在病毒发病机理和传播中的作用。 通过这些研究，我们旨在进一步了解IAV进化和潜在的因果关系机制。 希望有了更好地理解高度适应性的IAV，这些研究将发现新颖和改进的疫苗接种和打击IAV感染的方法。