Pathogenesis and Evolution of Influenza A Viruses in Swine

我的研究项目的首要目标是了解驱动甲型流感病毒（IAV）进化的遗传、流行病学和环境因素的影响，以及这些变化在其自然宿主之一中的生物学后果。******我的研究计划的长期目标是：***•确定与毒力和病毒在人群中地方性持续能力相关的遗传因素。***•确定个体和群体水平对猪流感病毒进化的影响和贡献，反之亦然。******在提出这个建议之前，我一直在通过在加拿大西部进行的监测活动从猪身上收集iav。这些从猪身上分离的IAV及其序列，以及相关的环境和流行病学数据（例如，发病率和死亡率信息、以前感染流感和其他疾病的情况、住房状况和生产状况），为拟议的工作提供了基础，并将继续为我的研究计划做出贡献。******关于进化驱动的基本生物学问题以及由此导致的iav生物学特性的改变将通过以下短期目标来解决：1)确定iav的进化关系；2)通过体外、离体和体内实验，发现天然氨基酸（AA）的插入和缺失对iav生物学特性的影响。******关于环境、流行病学和宿主压力如何驱动猪iav的遗传变化以及这些变化如何导致病毒在其自然宿主内的生物学特性发生变化，缺乏回答基本生物学问题的研究。尽管上个世纪对无人机进行了大量研究，但仍有许多问题需要回答。******我在猪流感方面的专业知识使我有资格回答这些问题并培养下一代高素质人才。除了我的流感专业知识外，我还是一名兽医病理学家，可以接触猪场、猪兽医和其他诊断专家。这使我有机会建立一个收集和鉴定猪流感病毒的网络，并在猪身上发现新的病毒。******我的研究项目将开发具有强大科学基础的新方法来评估流感病毒的毒力和发病机制，这将涉及本科生和研究生，以及病毒学和分子生物学基础和创新技术的博士后研究员，并回答有关流感病毒如何进化和引起疾病的令人信服的问题。

The overarching goal of my research program is to understand the impact of the genetic, epidemiological and environmental factors that drive influenza A virus (IAV) evolution and the biological consequences of these changes in one of its natural hosts. ******The long-term aims of my research program are:***• Identify genetic factors associated with virulence and the ability of a virus to be endemically sustained within a population. ***• Determine individual and population level consequences of and contributions to the evolution of influenza viruses in swine and vice versa.******Leading up to this proposal, I have been collecting IAVs from pigs through my ongoing surveillance activities in Western Canada. These IAV isolates from pigs and their sequences along with related environmental and epidemiological data (e.g., morbidity and mortality information, previous infections with flu and other diseases, housing status, and production status) provide a basis for the proposed work and will continue to contribute to my research program.******The fundamental biological questions on evolutionary drive and the resulting alterations in the biological properties of IAVs will be addressed through short-term objectives that will: 1) Determine evolutionary relationships of IAVs; and 2) Discover the effects of naturally occurring amino acid (AA) insertions and deletions on the biological properties of the IAVs through in-vitro, ex-vivo and in-vivo experiments. ******Research is lacking that answers the fundamental biological questions on how environmental, epidemiological and host pressures drive genetic change in swine IAVs and how these changes result in alterations in the biological properties of the virus within its natural host. For as much as IAVs have been studied over the last century, there are still many questions to answer.******My expertise of influenza in pigs makes me uniquely qualified to answer these questions and to train the next generation of highly qualified personnel. In addition to my influenza expertise, I am also a veterinary pathologist with access to swine farms, swine veterinarians and other diagnosticians. This has allowed me the opportunity to establish a network for collection and characterization of IAVs from pigs, and to discover new viruses in pigs. ****** My research program will develop novel approaches with a strong scientific foundation for assessing virulence and pathogenesis of influenza viruses that will involve undergraduate and graduate students, and post-doctoral fellows in basic and innovative techniques in virology and molecular biology, and answer compelling questions about how influenza viruses evolve and cause disease.