The effects of genetic bottlenecks on mutation fixation and replicative capacity of the influenza A virus

Microbiology;Avian Influenza Viruses;Mutation

Mamerow, MichaelWIlker, Peter ;

University of Wisconsin

关键词: Microbiology;    Avian Influenza Viruses;    Mutation;   

Others  :  https://minds.wisconsin.edu/bitstream/handle/1793/78856/Mamerow_Michael_Thesis.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: University of Wisconsin

【 摘 要 】

The influenza A virus is a common cause of respiratory illness in humans. Seasonalepidemics of influenza in the United States can result in up to 40 million cases, withannual hospitalizations and deaths reaching as high as 400,000 and 70,000, respectively.The influenza A virus continually causes annual epidemics, despite yearly vaccines, as aresult of its high mutation rate, leading to genetically diverse viral populations withinhosts. Respiratory droplet-mediated transmission of the virus between individuals isaccompanied by a bottleneck event that decreases the diversity of the viral populationpassed to new hosts. Using controlled artificial bottlenecks of different sizes during invitro serial passaging, the impact of these bottleneck events on patterns of mutationfixation and replicative capacity of the influenza A virus was determined. Growth curvesand genome sequencing were used after passaging to characterize differences inreplicative capacity and identify genomic changes within the population. Serial passagingat a bottleneck size of one virus generated virus populations with lower replicativecapacity as compared to the original parental virus. This effect was associated withfixation of numerous mutations spread throughout the genome. An increase in replicativecapacity was evident after repeated bottlenecks of 1000 viruses, demonstrating thatsufficiently loose bottlenecks do not compromise viral replication kinetics and even allowfor improvement. This increase in replicative capacity was associated with severalmutations, clustered primarily in the hemagglutinin genome segment.