Fig. 10

Hypothesis model of this study. Evolutionary selection has favored the 55C single nucleotide variant (SNV) trait of the M segment of the H1N1 virus, which promotes the splicing efficiency of M2 and consequent upregulation of M2 expression. While the 55C site changes to 55T, the splicing of M2 is inhibited, thereby leading to low M2 expression and impaired H1N1 virus replication. However, the H3N2-specific 55T variant results in low M2 protein expression. Even though the T55C trait can help express more H3N2 M2, it has no effect on the replication of the virus. Using chimeric viruses, low H3N2 M2 levels are enough to rescue the replication rate similar to that of wild-type H1N1 virus. However, excessive H3N2 M2 seems to be harmful for H1N1 virus. Noteworthily, SNVs can also show impact on the pathogenicity of influenza A viruses (IAVs) in vivo. 55T-typed H1N1 viruses showed the highest survival rate among all H1N1 viruses