Transmissibility of Influenza A Viruses

说明(由申请人提供)：该提案的长期目标是产生可用于准备或预防大流行性流感的知识。流感病毒的跨物种传播是产生大流行性流感毒株的关键因素。尽管人们对创造潜在的人类大流行毒株所需的分子步骤知之甚少，但中间宿主被认为是必要的。水禽是甲型流感病毒的天然宿主，但从香港人身上分离到的甲型流感病毒(1997年的H5N1和1999年的H9N2型)含有在陆上鸟类中传播和适应的基因，特别是在中国南部广泛饲养的鹌鹑。流行病学证据和我们的初步结果有力地表明，在能够跨越物种屏障的新型甲型流感病毒的出现中，鹌鹑可能在陆栖鸟类中发挥独特的作用。 这项拟议的研究将使用分子、经典病毒学和反向遗传学方法来确定1)陆上鸟类，特别是鹌鹑，作为中间宿主在甲型流感病毒跨物种传播和传播中的作用；2)甲型流感病毒在陆基禽类中间宿主中传播的分子基础。 随着全球家禽产量的增长(自20世纪60年代的S以来增长了200%以上)，如果要预防或充分准备应对大流行性流感毒株的出现，就必须阐明流感病毒跨物种传播的机制。获取这一信息所需的技术现已可用，结果将为农业政策和大流行规划的重要变化奠定基础。

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to generate knowledge that may be used to prepare for or prevent pandemic influenza. The interspecies transmission of influenza viruses is a key element in the generation of a pandemic influenza strain. Although little is known about the molecular steps required to create a potential human pandemic strain, intermediate hosts are considered necessary. Aquatic birds are the natural reservoir of influenza A viruses, but the influenza A viruses isolated from humans in Hong Kong (H5N1 in 1997 and H9N2 in1999) contained genes that had circulated and adapted in land-based birds, particularly quail, which are widely farmed in Southern China. Epidemiological evidence and our preliminary results strongly suggest that quail could play a unique role among land-based birds in the emergence of novel influenza A viruses that can cross the species barrier. The proposed research will use molecular, classical virologic, and reverse genetics methods to define 1) the role of land-based birds, particularly quail, as intermediate hosts in interspecies transmission and spread of influenza A viruses; and 2) the molecular basis of the transmissibility of influenza A viruses in land-based avian intermediate hosts. With poultry production increasing worldwide (more than 200% since the 1960's), the mechanisms underlying interspecies transmission of influenza viruses must be elucidated if the emergence of a pandemic influenza strain is to be forestalled or adequately prepared for. The techniques needed to obtain this information are now available, and the results will lay the groundwork for important changes in agricultural policies and pandemic planning.