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

The M-2 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 M-2 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 (M(2)Stop70) resulted in a virus that produced fourfold-fewer particles but > 1,000-fold-fewer infectious particles than wild-type virus. Expression of the full-length M-2 protein in trans restored the replication of the M-2 truncated virus. Although the M(2)Stop70 virus particles were similar to wild-type virus in morphology, the M(2)Stop70 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 efficient packaging of genome segments into influenza virus particles.