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Journal of Virology, March 2005, p. 3595-3605, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3595-3605.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Influenza A Virus M₂ Cytoplasmic Tail Is Required for Infectious Virus Production and Efficient Genome Packaging

Departments of Molecular Microbiology,¹ Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri²

Received 24 June 2004/ Accepted 21 October 2004

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 M₂ 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 full-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 M₂ cytoplasmic tail plays a role in infectious virus production by coordinating the efficient packaging of genome segments into influenza virus particles.

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