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Journal of Virology, June 2006, p. 5233-5240, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.00049-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

The Cytoplasmic Tail of the Influenza A Virus M2 Protein Plays a Role in Viral Assembly

Division of Virology, Department of Microbiology and Immunology,¹ International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639,³ Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012,² Department of Prion Diseases,⁴ Laboratory of Microbiology, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan,⁶ Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706⁵

Received 7 January 2006/ Accepted 8 March 2006

The viral replication cycle concludes with the assembly of viral components to form progeny virions. For influenza A viruses, the matrix M1 protein and two membrane integral glycoproteins, hemagglutinin and neuraminidase, function cooperatively in this process. Here, we asked whether another membrane protein, the M2 protein, plays a role in virus assembly. The M2 protein, comprising 97 amino acids, possesses the longest cytoplasmic tail (54 residues) of the three transmembrane proteins of influenza A viruses. We therefore generated a series of deletion mutants of the M2 cytoplasmic tail by reverse genetics. We found that mutants in which more than 22 amino acids were deleted from the carboxyl terminus of the M2 tail were viable but grew less efficiently than did the wild-type virus. An analysis of the virions suggested that viruses with M2 tail deletions of more than 22 carboxy-terminal residues apparently contained less viral ribonucleoprotein complex than did the wild-type virus. These M2 tail mutants also differ from the wild-type virus in their morphology: while the wild-type virus is spherical, some of the mutants were filamentous. Alanine-scanning experiments further indicated that amino acids at positions 74 to 79 of the M2 tail play a role in virion morphogenesis and affect viral infectivity. We conclude that the M2 cytoplasmic domain of influenza A viruses plays an important role in viral assembly and morphogenesis.

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