The influenza A virus M₂ cytoplasmic tail is required for infectious virus production and efficient genome packaging

The M₂ integral membrane protein encoded by influenza A virus possesses an ion channel activity that is required for efficient virus entry into host cells. The role of the M₂ protein cytoplasmic tail in virus replication was examined by generating influenza A viruses encoding M ₂ proteins with truncated C termini. Deletion of 28 amino acids (M₂Stop70) resulted in a virus that produced fourfold-fewer particles but >1,000-fold-fewer infectious particles than wild-type virus. Expression of the fall-length M₂ protein in trans restored the replication of the M₂ truncated virus. Although the M₂Stop70 virus particles were similar to wild-type virus in morphology, the M₂Stop70 virions contained reduced amounts of viral nucleoprotein and genomic RNA, indicating a defect in vRNP packaging. The data presented indicate the M ₂ cytoplasmic tail plays a role in infectious virus production by coordinating the effecient packaging of genome segments into influenza virus particles.