Reassortment of influenza viruses in a co-infected host

共感染宿主中流感病毒的重排

• 批准号: 8439377
• 负责人: Anice C Lowen
• 金额: $ 38.58万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8439377
• 关键词: Address; Aerosols; Affect; Animals; Antigenic Variation; Birds; Cavia; Cell Culture Techniques; Data; Disease Outbreaks; Epidemic; Epidemiologic Studies; Epidemiology; Event; Evolution; Family suidae; Ferrets; Frequencies; Gene Exchanges; Gene Pool; Generations; Genes; Genetic; Genome; Genotype; Growth; Housing; Human; Immune; Immunity; Infection; Influenza; Kinetics; Knowledge; MDCK cell; Mediating; Modeling; Mutation; Nature; Nucleotides; Play; Polymerase; Population; Predisposition; Process; Public Health; Reassortant Viruses; Recombinants; Relative (related person); Research; Role; Series; Severities; Site; Source; System; Testing; Time; Variant; Viral; Viral Genes; Viral Proteins; Virus; Virus Diseases; Work; cost; design; influenza epidemic; influenza virus gene; influenza virus strain; influenzavirus; insight; novel; pandemic disease; pandemic influenza; pressure; research study; seasonal influenza; time interval; transmission process

DESCRIPTION (provided by applicant): The recurring nature of influenza epidemics and pandemics is a consequence of the genetic and antigenic variability of the virus. This changeability in turn arises from mutations introduced by the error prone polymerase and the shuffling of viral gene segments among strains in the process of reassortment. The importance of reassortment among human and animal influenza viruses to the genesis of pandemic strains has been appreciated for many years. More recent phylogenic and epidemiological studies have furthermore established a significant role for reassortment between seasonal influenza viruses in the generation of novel epidemic strains. Nevertheless, little is known about how efficiently and under what circumstances reassortment occurs in a host co-infected with two influenza viruses. Through the proposed research we plan to address this gap in knowledge. Using both cell culture and guinea pig models, we will first determine the frequency with which reassortment occurs in the absence of selective pressures. We will then introduce systematically a number of variables, such as pre-existing immunity or a time interval between infections, and determine whether each increases or decreases the number of reassortant progeny arising from the co-infection. In this way, we will establish the parameters that govern the process of influenza virus reassortment. Since reassortant strains will be epidemiologically significant only if they are transmitted to additional hosts, we will also evaluate the size of the bottleneck created by influenza virus transmission. Thus, through carefully controlled experimental studies, we propose to reveal novel insights in the mechanisms governing influenza virus evolution and the emergence of epidemic and pandemic strains. PUBLIC HEALTH RELEVANCE: Through regular epidemics and infrequent pandemics, influenza affects a significant proportion of the population every year. Reassortment, the process by which two differing influenza viruses exchange genes, is one mechanism by which antigenically novel strains capable of causing these outbreaks arise. By defining the circumstances under which reassortment can proceed, our proposed research will enable public health efforts aimed at predicting and limiting the emergence of new influenza virus strains. !!

描述（由申请方提供）：流感流行和大流行的重复性是病毒遗传和抗原变异性的结果。这种可变性反过来又是由易错聚合酶引入的突变和病毒基因片段在重配过程中在毒株之间的改组引起的。人类和动物流感病毒之间的重配对大流行毒株的发生的重要性多年来一直受到重视。最近的遗传学和流行病学研究进一步确定了季节性流感病毒之间的重配在产生新的流行毒株中的重要作用。然而，很少有人知道如何有效地和在什么情况下发生的重组在一个主机共感染两种流感病毒。通过拟议的研究，我们计划解决这一知识差距。使用细胞培养和豚鼠模型，我们将首先确定在没有选择压力的情况下发生重配的频率。然后，我们将系统地引入一些变量，如预先存在的免疫力或感染之间的时间间隔，并确定每个是否增加或减少由共感染产生的reflectant后代的数量。通过这种方式，我们将建立控制流感病毒重配过程的参数。由于只有当它们传播给其他宿主时，才具有流行病学意义，我们还将评估 流感病毒传播的瓶颈。因此，通过精心控制的实验研究，我们建议揭示新的见解的机制，流感病毒的进化和流行和大流行株的出现。 公共卫生相关性：通过定期流行和罕见的大流行，流感每年影响很大一部分人口。重配是两种不同的流感病毒交换基因的过程，是能够引起这些爆发的抗原性新毒株出现的一种机制。通过确定重配可以进行的情况，我们提出的研究将使公共卫生工作能够预测和限制新流感病毒株的出现。!!