This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hatta, M.
Right arrow Articles by Kawaoka, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hatta, M.
Right arrow Articles by Kawaoka, Y.

 Previous Article  |  Next Article 

Journal of Virology, June 2004, p. 5576-5583, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5576-5583.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Influenza B Virus Requires BM2 Protein for Replication

Masato Hatta,1 Hideo Goto,2 and Yoshihiro Kawaoka1,2,3*

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin—Madison, Madison, Wisconsin 53706,1 Institute of Medical Science, University of Tokyo, Tokyo 108-8639,2 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan3

Received 29 September 2003/ Accepted 26 January 2004

The BM2 protein of influenza B virus functions as an ion channel, which is suggested to be important for virus uncoating in endosomes of virus-infected cells. Because direct support for this function is lacking, whether BM2 plays an essential role in the viral life cycle remains unknown. We therefore attempted to generate BM2 knockout viruses by reverse genetics. Mutant viruses possessing M segments with the mutated initiation codon of BM2 protein at the stop-start pentanucleotide were viable and still expressed BM2. The introduction of multiple stop codons and a one-nucleotide deletion downstream of the stop-start pentanucleotide, in addition to disablement of the BM2 initiation codon, failed to generate viable mutant viruses, but the mutant M segments still expressed proteins that reacted with the BM2 peptide antiserum. To completely abolish BM2 expression, we generated a mutant M gene whose BM2 open reading frame was deleted. Although this mutant was not able to replicate in normal MDCK cells, it did replicate in a cell line that we established which constitutively expresses BM2. Furthermore, a virus possessing the mutant M gene lacking the BM2 open reading frame and a mutant NA gene containing the BM2 open reading frame instead of the NA open reading frame underwent multiple cycles of replication in MDCK cells, with exogenous sialidase used to supplement the deleted viral sialidase activity. These findings demonstrate that the BM2 protein is essential for influenza B virus replication.

* Corresponding author. Mailing address: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706. Phone: (608) 265-1925. Fax: (608) 265-5622. E-mail: kawaokay{at}svm.vetmed.wisc.edu.

Journal of Virology, June 2004, p. 5576-5583, Vol. 78, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.11.5576-5583.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hatta, M., Kohlmeier, C. K., Hatta, Y., Ozawa, M., Kawaoka, Y. (2009). Region Required for Protein Expression from the Stop-Start Pentanucleotide in the M Gene of Influenza B Virus. J. Virol. 83: 5939-5942 [Abstract] [Full Text]  
  • Otomo, K., Toyama, A., Miura, T., Takeuchi, H. (2009). Interactions Between Histidine and Tryptophan Residues in the BM2 Proton Channel from Influenza B Virus. J Biochem 145: 543-554 [Abstract] [Full Text]  
  • Ma, C., Soto, C. S., Ohigashi, Y., Taylor, A., Bournas, V., Glawe, B., Udo, M. K., DeGrado, W. F., Lamb, R. A., Pinto, L. H. (2008). Identification of the Pore-lining Residues of the BM2 Ion Channel Protein of Influenza B Virus. J. Biol. Chem. 283: 15921-15931 [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]  
  • 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]  
  • McCown, M. F., Pekosz, A. (2005). The Influenza A Virus M2 Cytoplasmic Tail Is Required for Infectious Virus Production and Efficient Genome Packaging. J. Virol. 79: 3595-3605 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»