Pathogenesis and Evolution of Influenza A Viruses in Swine

我的研究计划的总体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持续流行的能力相关的遗传因素。 确定猪流感病毒进化的个体和群体水平的后果和贡献，反之亦然。导致这一建议，我一直在收集IAV从猪通过我在加拿大西部正在进行的监测活动。这些来自猪的IAV分离物及其序列沿着相关的环境和流行病学数据（例如，发病率和死亡率的信息，以前感染流感和其他疾病，住房状况，和生产状况）提供了一个基础，为拟议的工作，并将继续有助于我的研究计划，基本的生物学问题的进化驱动和由此产生的改变的生物学特性的IAV将通过短期目标，将解决：1）确定IAV的进化关系; 2）通过体外、离体和体内实验，研究天然氨基酸（AA）插入和缺失对IAV生物学特性的影响。 目前缺乏研究来回答以下基本生物学问题：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改变。尽管IAV在上个世纪已经被研究了很多，但仍然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的人才。除了我的流感专业知识，我也是一名兽医病理学家，可以接触养猪场，猪兽医和其他诊断医生。这使我有机会建立一个收集和表征猪IAV的网络，并发现猪中的新病毒。 我的研究计划将开发具有强大科学基础的新方法，用于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.