Previous Article | Next Article 
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
Matthew F. McCown1 and
Andrew Pekosz1,2*
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.
* Corresponding author. Mailing address: Department of Molecular Microbiology, Washington University School of Medicine, Campus Box 8230, 660 S. Euclid Ave., St. Louis, MO 63110-1093. Phone: (314) 747-2132. Fax: (314) 362-3203. E-mail:
pekosz{at}borcim.wustl.edu.
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.
This article has been cited by other articles:
-
Grantham, M. L., Wu, W.-H., Lalime, E. N., Lorenzo, M. E., Klein, S. L., Pekosz, A.
(2009). Palmitoylation of the Influenza A Virus M2 Protein Is Not Required for Virus Replication In Vitro but Contributes to Virus Virulence. J. Virol.
83: 8655-8661
[Abstract]
[Full Text]
-
Lee, H. Y., Topham, D. J., Park, S. Y., Hollenbaugh, J., Treanor, J., Mosmann, T. R., Jin, X., Ward, B. M., Miao, H., Holden-Wiltse, J., Perelson, A. S., Zand, M., Wu, H.
(2009). Simulation and Prediction of the Adaptive Immune Response to Influenza A Virus Infection. J. Virol.
83: 7151-7165
[Abstract]
[Full Text]
-
Watanabe, S., Watanabe, T., Kawaoka, Y.
(2009). Influenza A Virus Lacking M2 Protein as a Live Attenuated Vaccine. J. Virol.
83: 5947-5950
[Abstract]
[Full Text]
-
Noton, S. L., Simpson-Holley, M., Medcalf, E., Wise, H. M., Hutchinson, E. C., McCauley, J. W., Digard, P.
(2009). Studies of an Influenza A Virus Temperature-Sensitive Mutant Identify a Late Role for NP in the Formation of Infectious Virions. J. Virol.
83: 562-571
[Abstract]
[Full Text]
-
Hutchinson, E. C., Curran, M. D., Read, E. K., Gog, J. R., Digard, P.
(2008). Mutational Analysis of cis-Acting RNA Signals in Segment 7 of Influenza A Virus. J. Virol.
82: 11869-11879
[Abstract]
[Full Text]
-
Chen, B. J., Leser, G. P., Jackson, D., Lamb, R. A.
(2008). The Influenza Virus M2 Protein Cytoplasmic Tail Interacts with the M1 Protein and Influences Virus Assembly at the Site of Virus Budding. J. Virol.
82: 10059-10070
[Abstract]
[Full Text]
-
Watanabe, T., Watanabe, S., Kim, J. H., Hatta, M., Kawaoka, Y.
(2008). Novel Approach to the Development of Effective H5N1 Influenza A Virus Vaccines: Use of M2 Cytoplasmic Tail Mutants. J. Virol.
82: 2486-2492
[Abstract]
[Full Text]
-
Imai, M., Kawasaki, K., Odagiri, T.
(2008). Cytoplasmic Domain of Influenza B Virus BM2 Protein Plays Critical Roles in Production of Infectious Virus. J. Virol.
82: 728-739
[Abstract]
[Full Text]
-
Wu, W.-H., Pekosz, A.
(2008). Extending the Cytoplasmic Tail of the Influenza A Virus M2 Protein Leads to Reduced Virus Replication In Vivo but Not In Vitro. J. Virol.
82: 1059-1063
[Abstract]
[Full Text]
-
Schaecher, S. R., Touchette, E., Schriewer, J., Buller, R. M., Pekosz, A.
(2007). Severe Acute Respiratory Syndrome Coronavirus Gene 7 Products Contribute to Virus-Induced Apoptosis. J. Virol.
81: 11054-11068
[Abstract]
[Full Text]
-
Newby, C. M., Sabin, L., Pekosz, A.
(2007). The RNA Binding Domain of Influenza A Virus NS1 Protein Affects Secretion of Tumor Necrosis Factor Alpha, Interleukin-6, and Interferon in Primary Murine Tracheal Epithelial Cells. J. Virol.
81: 9469-9480
[Abstract]
[Full Text]
-
Chen, B. J., Leser, G. P., Morita, E., Lamb, R. A.
(2007). Influenza Virus Hemagglutinin and Neuraminidase, but Not the Matrix Protein, Are Required for Assembly and Budding of Plasmid-Derived Virus-Like Particles. J. Virol.
81: 7111-7123
[Abstract]
[Full Text]
-
Lenschow, D. J., Lai, C., Frias-Staheli, N., Giannakopoulos, N. V., Lutz, A., Wolff, T., Osiak, A., Levine, B., Schmidt, R. E., Garcia-Sastre, A., Leib, D. A., Pekosz, A., Knobeloch, K.-P., Horak, I., Virgin, H. W. IV
(2007). From the cover: IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. Proc. Natl. Acad. Sci. USA
104: 1371-1376
[Abstract]
[Full Text]
-
Schaecher, S. R., Mackenzie, J. M., Pekosz, A.
(2007). The ORF7b Protein of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Is Expressed in Virus-Infected Cells and Incorporated into SARS-CoV Particles. J. Virol.
81: 718-731
[Abstract]
[Full Text]
-
Ibricevic, A., Pekosz, A., Walter, M. J., Newby, C., Battaile, J. T., Brown, E. G., Holtzman, M. J., Brody, S. L.
(2006). Influenza virus receptor specificity and cell tropism in mouse and human airway epithelial cells.. J. Virol.
80: 7469-7480
[Abstract]
[Full Text]
-
McCown, M. F., Pekosz, A.
(2006). Distinct domains of the influenza a virus m2 protein cytoplasmic tail mediate binding to the m1 protein and facilitate infectious virus production.. J. Virol.
80: 8178-8189
[Abstract]
[Full Text]
-
Iwatsuki-Horimoto, K., Horimoto, T., Noda, T., Kiso, M., Maeda, J., Watanabe, S., Muramoto, Y., Fujii, K., Kawaoka, Y.
(2006). The cytoplasmic tail of the influenza a virus m2 protein plays a role in viral assembly.. J. Virol.
80: 5233-5240
[Abstract]
[Full Text]
-
Rowe, R. K., Pekosz, A.
(2006). Bidirectional Virus Secretion and Nonciliated Cell Tropism following Andes Virus Infection of Primary Airway Epithelial Cell Cultures. J. Virol.
80: 1087-1097
[Abstract]
[Full Text]