This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
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 Jiao, P.
Right arrow Articles by Chen, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jiao, P.
Right arrow Articles by Chen, H.

 Previous Article  |  Next Article 

Journal of Virology, February 2008, p. 1146-1154, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01698-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice{triangledown}

Peirong Jiao,1 Guobin Tian,1 Yanbing Li,1 Guohua Deng,1 Yongping Jiang,1 Chang Liu,1 Weilong Liu,1 Zhigao Bu,1 Yoshihiro Kawaoka,2,3,4 and Hualan Chen1*

Animal Influenza Laboratory of the Ministry of Agriculture and National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Harbin 150001, People's Republic of China,1 Division of Virology, Department of Microbiology and Immunology,2 International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan,3 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 537064

Received 6 August 2007/ Accepted 6 November 2007

In this study, we explored the molecular basis determining the virulence of H5N1 avian influenza viruses in mammalian hosts by comparing two viruses, A/Duck/Guangxi/12/03 (DK/12) and A/Duck/Guangxi/27/03 (DK/27), which are genetically similar but differ in their pathogenicities in mice. To assess the genetic basis for this difference in virulence, we used reverse genetics to generate a series of reassortants and mutants of these two viruses. We found that a single-amino-acid substitution of serine for proline at position 42 (P42S) in the NS1 protein dramatically increased the virulence of the DK/12 virus in mice, whereas the substitution of proline for serine at the same position (S42P) completely attenuated the DK/27 virus. We further demonstrated that the amino acid S42 of NS1 is critical for the H5N1 influenza virus to antagonize host cell interferon induction and for the NS1 protein to prevent the double-stranded RNA-mediated activation of the NF-{kappa}B pathway and the IRF-3 pathway. Our results indicate that the NS1 protein is critical for the pathogenicity of H5N1 influenza viruses in mammalian hosts and that the amino acid S42 of NS1 plays a key role in undermining the antiviral immune response of the host cell.

* Corresponding author. Mailing address: Harbin Veterinary Research Institute, CAAS, 427 Maduan Street, Harbin 150001, People's Republic of China. Phone: 86-451-85935079. Fax: 86-451-82733132. E-mail: hlchen1{at}yahoo.com

{triangledown} Published ahead of print on 21 November 2007.

Journal of Virology, February 2008, p. 1146-1154, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01698-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lycett, S. J., Ward, M. J., Lewis, F. I., Poon, A. F. Y., Kosakovsky Pond, S. L., Brown, A. J. L. (2009). Detection of Mammalian Virulence Determinants in Highly Pathogenic Avian Influenza H5N1 Viruses: Multivariate Analysis of Published Data. J. Virol. 83: 9901-9910 [Abstract] [Full Text]  
  • Gabriel, G., Klingel, K., Planz, O., Bier, K., Herwig, A., Sauter, M., Klenk, H.-D. (2009). Spread of Infection and Lymphocyte Depletion in Mice Depends on Polymerase of Influenza Virus. Am. J. Pathol. 175: 1178-1186 [Abstract] [Full Text]  
  • Szretter, K. J., Gangappa, S., Belser, J. A., Zeng, H., Chen, H., Matsuoka, Y., Sambhara, S., Swayne, D. E., Tumpey, T. M., Katz, J. M. (2009). Early Control of H5N1 Influenza Virus Replication by the Type I Interferon Response in Mice. J. Virol. 83: 5825-5834 [Abstract] [Full Text]  
  • Stech, O., Veits, J., Weber, S., Deckers, D., Schroer, D., Vahlenkamp, T. W., Breithaupt, A., Teifke, J., Mettenleiter, T. C., Stech, J. (2009). Acquisition of a Polybasic Hemagglutinin Cleavage Site by a Low-Pathogenic Avian Influenza Virus Is Not Sufficient for Immediate Transformation into a Highly Pathogenic Strain. J. Virol. 83: 5864-5868 [Abstract] [Full Text]  
  • Heltzer, M. L., Coffin, S. E., Maurer, K., Bagashev, A., Zhang, Z., Orange, J. S., Sullivan, K. E. (2009). Immune dysregulation in severe influenza. J. Leukoc. Biol. 85: 1036-1043 [Abstract] [Full Text]  
  • Hale, B. G., Randall, R. E., Ortin, J., Jackson, D. (2008). The multifunctional NS1 protein of influenza A viruses. J. Gen. Virol. 89: 2359-2376 [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»