Pathogenesis and Evolution of Influenza A Viruses in Swine

猪甲型流感病毒的发病机制和进化

• 批准号: RGPIN-2018-05152
• 负责人: Detmer, Susan
• 金额: $ 3.06万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=713514
• 关键词: Pathogenesis; Evolution; Influenza; Viruses; Swine

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.

我的研究计划的总体目标是了解驱动流感病毒（IAV）进化的遗传，流行病学和环境因素的影响，以及在其自然宿主之一中这些变化的生物学后果。 我的研究计划的长期目标是： 鉴定与毒力相关的遗传因素以及在人群中维持病毒的能力。 确定个人和人口水平的后果，以及对猪流感病毒进化的贡献，反之亦然。 在提出这一建议之前，我一直在加拿大西部正在进行的监视活动中从猪那里收集IAV。这些IAV从猪及其序列中分离出来，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，以前的流感和其他疾病感染，住房状况和生产状态）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IAV的生物学特性的改变，将通过短期目标来解决：1）确定IAV的进化关系； 2）发现天然存在的氨基酸（AA）插入和缺失对通过体外，前体和体内实验的IAV的生物学特性的影响。 研究缺乏回答有关环境，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自然宿主中病毒生物学特性改变的基本生物学问题。在上个世纪，就已经研究了IAV，还有很多问题要回答。 我在猪中流感的专业知识使我有资格回答这些问题并培训下一代高素质的人员。除了我的流感专业知识外，我还是兽医病理学家，可以使用猪农场，猪兽医和其他诊断师。这使我有机会建立一个网络，以收集和表征猪的IAV，并发现猪中的新病毒。 我的研究计划将开发出具有良好科学基础的新方法，以评估涉及本科生和研究生的流感病毒的毒力和发病机理，以及在病毒学和分子生物学中基本和创新技术中的博士后研究员，并回答有关流感病毒进化和引起疾病的令人信服的问题。