Reassortment of influenza viruses in a co-infected host

共感染宿主中流感病毒的重排

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：流感流行和大流行的反复发生是病毒遗传和抗原变异性的结果。这种可变性又是由容易出错的聚合酶引入的突变以及重配过程中病毒株之间病毒基因片段的改组引起的。多年来，人类和动物流感病毒之间的重配对于大流行毒株发生的重要性已得到认识。最近的系统发生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新型流行毒株的产生中的重要作用。然而，对于同时感染两种流感病毒的宿主中重配发生的效率和在什么情况下发生的情况知之甚少。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重配发生的频率。然后，我们将系统地引入许多变量，例如预先存在的免疫力或感染之间的时间间隔，并确定每个变量是否会增加或减少因共同感染而产生的重配后代的数量。通过这种方式，我们将建立控制流感病毒重配过程的参数。由于重配菌株只有在传播到其他宿主时才会具有流行病学意义，因此我们还将评估重配菌株的大小流感病毒传播造成的瓶颈。因此，通过仔细控制的实验研究，我们建议揭示有关流感病毒进化和流行性和大流行毒株出现的机制的新见解。公共卫生相关性：通过定期流行和罕见的大流行，流感每年都会影响很大一部分人口。重配是两种不同流感病毒交换基因的过程，是能够引起这些疫情的抗原性新毒株出现的一种机制。通过定义可以进行重配的情况，我们提出的研究将使旨在预测和限制新流感病毒株出现的公共卫生工作成为可能。 !!