Dysregulation of M segment gene expression contributes to influenza A virus host restriction
Fig 16
Regulation of M segment gene expression contributes to host range restriction of IAV.
When an avian IAV M segment is transcribed within mammalian cells, excessive splicing of mRNA7 results in aberrant overexpression of the M2 proton channel. When highly expressed, this channel accumulates in autophagic vesicles. Abundant proton channel activity in the membranes of autophagosomes blocks their turnover by preventing fusion with lysosomes. This stalling of a critical cellular housekeeping function in turn reduces the efficiency of viral replication, contributing to the species barrier that limits the zoonotic potential of avian IAVs.