Characterization of Mutations in the C-Terminal Domain of the NS1 Protein of Influenza A Viruses and Live Attenuated Influenza Vaccine
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Influenza virus is one of the most pervasive pathogenic threats to the global public health on an annual basis. Each year, this RNA virus causes hundreds of thousands of deaths and billions of dollars in economic damage. The influenza vaccine is a key contributor in the fight against influenza infection and is available in several formulations, including the Live Attenuated Influenza Vaccine (LAIV). Although LAIV was sequenced nearly 20 years ago, the role of some of its genomic mutations have yet to be characterized. I believe the NS gene segment contributes to the attenuation phenotype of LAIV. To test this hypothesis, a panel of NS reassortant viruses in both the LAIV and A/Victoria/361/2011 backbones were generated. Additionally, a panel of recombinant viruses expressing a mutation at amino acid residue position 153 in the non-structural protein 1 (NS1) C-terminal domain were generated in both the LAIV and A/Victoria/361/2011 backbones. The NS reassortant viruses were generated, sequence verified, and characterized in MDCK and A549 cell culture systems. We show that a reassortant virus with LAIV NS in the A/Victoria/361/2011 backbone display faster growth kinetics in MDCK and A549 cell systems than its wild-type NS counterpart in the A/Victoria/361/2011 backbone. In MDCK cells, a reassortant virus with LAIV NS in the LAIV backbone displayed faster growth kinetics than a reassortant LAIV virus with wild-type NS. However, there was no significant difference in A549 cells. These data indicate the NS gene segment of influenza has a role in viral replication.