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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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