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Journal of Virology, June 2001, p. 5656-5662, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5656-5662.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Influenza A Virus Can Undergo Multiple Cycles of Replication without M2 Ion Channel Activity

Tokiko Watanabe,1,2 Shinji Watanabe,1 Hiroshi Ito,1 Hiroshi Kida,2 and Yoshihiro Kawaoka1,3,*

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706,1 and Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818,2 and Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639,3 Japan

Received 29 December 2000/Accepted 21 March 2001

Ion channel proteins are common constituents of cells and have even been identified in some viruses. For example, the M2 protein of influenza A virus has proton ion channel activity that is thought to play an important role in viral replication. Because direct support for this function is lacking, we attempted to generate viruses with defective M2 ion channel activity. Unexpectedly, mutants with apparent loss of M2 ion channel activity by an in vitro assay replicated as efficiently as the wild-type virus in cell culture. We also generated a chimeric mutant containing an M2 protein whose transmembrane domain was replaced with that from the hemagglutinin glycoprotein. This virus replicated reasonably well in cell culture but showed no growth in mice. Finally, a mutant lacking both the transmembrane and cytoplasmic domains of M2 protein grew poorly in cell culture and showed no growth in mice. Thus, influenza A virus can undergo multiple cycles of replication without the M2 transmembrane domain responsible for ion channel activity, although this activity promotes efficient viral replication.

* Corresponding author. Mailing address: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive West, Madison, WI 53706. Phone: (608) 265-4925. Fax: (608) 265-5622. E-mail: kawaokay{at}svm.vetmed.wisc.edu.

Journal of Virology, June 2001, p. 5656-5662, Vol. 75, No. 12
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.12.5656-5662.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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