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 Mibayashi, M.
Right arrow Articles by García-Sastre, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mibayashi, M.
Right arrow Articles by García-Sastre, A.

 Previous Article  |  Next Article 

Journal of Virology, January 2007, p. 514-524, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01265-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Inhibition of Retinoic Acid-Inducible Gene I-Mediated Induction of Beta Interferon by the NS1 Protein of Influenza A Virus{triangledown}

Masaki Mibayashi,1 Luis Martínez-Sobrido,1 Yueh-Ming Loo,2 Washington B. Cárdenas,1 Michael Gale Jr.,2 and Adolfo García-Sastre1*

Department of Microbiology, Mount Sinai School of Medicine, New York, New York,1 Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas2

Received 16 June 2006/ Accepted 23 October 2006

The retinoic acid-inducible gene I product (RIG-I) has been identified as a cellular sensor of RNA virus infection resulting in beta interferon (IFN-ß) induction. However, many viruses are known to encode viral products that inhibit IFN-ß production. In the case of influenza A virus, the viral nonstructural protein 1 (NS1) prevents the induction of the IFN-ß promoter by inhibiting the activation of transcription factors, including IRF-3, involved in IFN-ß transcriptional activation. The inhibitory properties of NS1 appear to be due at least in part to its binding to double-stranded RNA (dsRNA), resulting in the sequestration of this viral mediator of RIG-I activation. However, the precise effects of NS1 on the RIG-I-mediated induction of IFN-ß have not been characterized. We now report that the NS1 of influenza A virus interacts with RIG-I and inhibits the RIG-I-mediated induction of IFN-ß. This inhibition was apparent even when a mutant RIG-I that is constitutively activated (in the absence of dsRNA) was used to trigger IFN-ß production. Coexpression of RIG-I, its downstream signaling partner, IPS-1, and NS1 resulted in increased levels of RIG-I and NS1 within an IPS-1-rich, solubilization-resistant fraction after cell lysis. These results suggest that RIG-I, IPS-1, and NS1 become part of the same complex. Consistent with this idea, NS1 was also found to inhibit IFN-ß promoter activation by IPS-1 overexpression. Our results indicate that, in addition to sequestering dsRNA, the NS1 of influenza A virus binds to RIG-I and inhibits downstream activation of IRF-3, preventing the transcriptional induction of IFN-ß.

* Corresponding author. Mailing address: Department of Microbiology, Box 1124, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029. Phone: (212) 241-7769. Fax: (212) 534-1684. E-mail: adolfo.garcia-sastre{at}mssm.edu.

{triangledown} Published ahead of print on 1 November 2006.

Journal of Virology, January 2007, p. 514-524, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01265-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • de Vries, W., Haasnoot, J., Fouchier, R., de Haan, P., Berkhout, B. (2009). Differential RNA silencing suppression activity of NS1 proteins from different influenza A virus strains. J. Gen. Virol. 90: 1916-1922 [Abstract] [Full Text]  
  • Haye, K., Burmakina, S., Moran, T., Garcia-Sastre, A., Fernandez-Sesma, A. (2009). The NS1 Protein of a Human Influenza Virus Inhibits Type I Interferon Production and the Induction of Antiviral Responses in Primary Human Dendritic and Respiratory Epithelial Cells. J. Virol. 83: 6849-6862 [Abstract] [Full Text]  
  • Siu, K.-L., Kok, K.-H., Ng, M.-H. J., Poon, V. K. M., Yuen, K.-Y., Zheng, B.-J., Jin, D.-Y. (2009). Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3{middle dot}TANK{middle dot}TBK1/IKK{epsilon} Complex. J. Biol. Chem. 284: 16202-16209 [Abstract] [Full Text]  
  • Ling, Z., Tran, K. C., Teng, M. N. (2009). Human Respiratory Syncytial Virus Nonstructural Protein NS2 Antagonizes the Activation of Beta Interferon Transcription by Interacting with RIG-I. J. Virol. 83: 3734-3742 [Abstract] [Full Text]  
  • Mogensen, T. H. (2009). Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses. Clin. Microbiol. Rev. 22: 240-273 [Abstract] [Full Text]  
  • Kakugawa, S., Shimojima, M., Goto, H., Horimoto, T., Oshimori, N., Neumann, G., Yamamoto, T., Kawaoka, Y. (2009). Mitogen-Activated Protein Kinase-Activated Kinase RSK2 Plays a Role in Innate Immune Responses to Influenza Virus Infection. J. Virol. 83: 2510-2517 [Abstract] [Full Text]  
  • Baskin, C. R., Bielefeldt-Ohmann, H., Tumpey, T. M., Sabourin, P. J., Long, J. P., Garcia-Sastre, A., Tolnay, A.-E., Albrecht, R., Pyles, J. A., Olson, P. H., Aicher, L. D., Rosenzweig, E. R., Murali-Krishna, K., Clark, E. A., Kotur, M. S., Fornek, J. L., Proll, S., Palermo, R. E., Sabourin, C. L., Katze, M. G. (2009). Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus. Proc. Natl. Acad. Sci. USA 106: 3455-3460 [Abstract] [Full Text]  
  • Basu, D., Walkiewicz, M. P., Frieman, M., Baric, R. S., Auble, D. T., Engel, D. A. (2009). Novel Influenza Virus NS1 Antagonists Block Replication and Restore Innate Immune Function. J. Virol. 83: 1881-1891 [Abstract] [Full Text]  
  • Schneider, J., Dauber, B., Melen, K., Julkunen, I., Wolff, T. (2009). Analysis of Influenza B Virus NS1 Protein Trafficking Reveals a Novel Interaction with Nuclear Speckle Domains. J. Virol. 83: 701-711 [Abstract] [Full Text]  
  • Vogt, C., Preuss, E., Mayer, D., Weber, F., Schwemmle, M., Kochs, G. (2008). The Interferon Antagonist ML Protein of Thogoto Virus Targets General Transcription Factor IIB. J. Virol. 82: 11446-11453 [Abstract] [Full Text]  
  • Borderia, A. V., Hartmann, B. M., Fernandez-Sesma, A., Moran, T. M., Sealfon, S. C. (2008). Antiviral-Activated Dendritic Cells: A Paracrine-Induced Response State. J. Immunol. 181: 6872-6881 [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]  
  • Alff, P. J., Sen, N., Gorbunova, E., Gavrilovskaya, I. N., Mackow, E. R. (2008). The NY-1 Hantavirus Gn Cytoplasmic Tail Coprecipitates TRAF3 and Inhibits Cellular Interferon Responses by Disrupting TBK1-TRAF3 Complex Formation. J. Virol. 82: 9115-9122 [Abstract] [Full Text]  
  • Nakatsu, Y., Takeda, M., Ohno, S., Shirogane, Y., Iwasaki, M., Yanagi, Y. (2008). Measles Virus Circumvents the Host Interferon Response by Different Actions of the C and V Proteins. J. Virol. 82: 8296-8306 [Abstract] [Full Text]  
  • Bitko, V., Musiyenko, A., Bayfield, M. A., Maraia, R. J., Barik, S. (2008). Cellular La Protein Shields Nonsegmented Negative-Strand RNA Viral Leader RNA from RIG-I and Enhances Virus Growth by Diverse Mechanisms. J. Virol. 82: 7977-7987 [Abstract] [Full Text]  
  • Kimura, R., Ohashi, J., Matsumura, Y., Nakazawa, M., Inaoka, T., Ohtsuka, R., Osawa, M., Tokunaga, K. (2008). Gene Flow and Natural Selection in Oceanic Human Populations Inferred from Genome-Wide SNP Typing. Mol Biol Evol 25: 1750-1761 [Abstract] [Full Text]  
  • Lu, L. L., Puri, M., Horvath, C. M., Sen, G. C. (2008). Select Paramyxoviral V Proteins Inhibit IRF3 Activation by Acting as Alternative Substrates for Inhibitor of {kappa}B Kinase {epsilon} (IKKe)/TBK1. J. Biol. Chem. 283: 14269-14276 [Abstract] [Full Text]  
  • Davis, A. M., Hagan, K. A., Matthews, L. A., Bajwa, G., Gill, M. A., Gale, M. Jr., Farrar, J. D. (2008). Blockade of Virus Infection by Human CD4+ T Cells via a Cytokine Relay Network. J. Immunol. 180: 6923-6932 [Abstract] [Full Text]  
  • Jackson, D., Hossain, Md. J., Hickman, D., Perez, D. R., Lamb, R. A. (2008). A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity. Proc. Natl. Acad. Sci. USA 105: 4381-4386 [Abstract] [Full Text]  
  • Jiao, P., Tian, G., Li, Y., Deng, G., Jiang, Y., Liu, C., Liu, W., Bu, Z., Kawaoka, Y., Chen, H. (2008). A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice. J. Virol. 82: 1146-1154 [Abstract] [Full Text]  
  • Kim, M.-J., Hwang, S.-Y., Imaizumi, T., Yoo, J.-Y. (2008). Negative Feedback Regulation of RIG-I-Mediated Antiviral Signaling by Interferon-Induced ISG15 Conjugation. J. Virol. 82: 1474-1483 [Abstract] [Full Text]  
  • Randall, R. E., Goodbourn, S. (2008). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89: 1-47 [Abstract] [Full Text]  
  • Loo, Y.-M., Fornek, J., Crochet, N., Bajwa, G., Perwitasari, O., Martinez-Sobrido, L., Akira, S., Gill, M. A., Garcia-Sastre, A., Katze, M. G., Gale, M. Jr. (2008). Distinct RIG-I and MDA5 Signaling by RNA Viruses in Innate Immunity. J. Virol. 82: 335-345 [Abstract] [Full Text]  
  • Shin, Y.-K., Li, Y., Liu, Q., Anderson, D. H., Babiuk, L. A., Zhou, Y. (2007). SH3 Binding Motif 1 in Influenza A Virus NS1 Protein Is Essential for PI3K/Akt Signaling Pathway Activation. J. Virol. 81: 12730-12739 [Abstract] [Full Text]  
  • Strahle, L., Marq, J.-B., Brini, A., Hausmann, S., Kolakofsky, D., Garcin, D. (2007). Activation of the Beta Interferon Promoter by Unnatural Sendai Virus Infection Requires RIG-I and Is Inhibited by Viral C Proteins. J. Virol. 81: 12227-12237 [Abstract] [Full Text]  
  • Martinez-Sobrido, L., Giannakas, P., Cubitt, B., Garcia-Sastre, A., de la Torre, J. C. (2007). Differential Inhibition of Type I Interferon Induction by Arenavirus Nucleoproteins. J. Virol. 81: 12696-12703 [Abstract] [Full Text]  
  • Waibler, Z., Anzaghe, M., Ludwig, H., Akira, S., Weiss, S., Sutter, G., Kalinke, U. (2007). Modified Vaccinia Virus Ankara Induces Toll-Like Receptor-Independent Type I Interferon Responses. J. Virol. 81: 12102-12110 [Abstract] [Full Text]  
  • Zeng, H., Goldsmith, C., Thawatsupha, P., Chittaganpitch, M., Waicharoen, S., Zaki, S., Tumpey, T. M., Katz, J. M. (2007). Highly Pathogenic Avian Influenza H5N1 Viruses Elicit an Attenuated Type I Interferon Response in Polarized Human Bronchial Epithelial Cells. J. Virol. 81: 12439-12449 [Abstract] [Full Text]  
  • Baskin, C. R., Bielefeldt-Ohmann, H., Garcia-Sastre, A., Tumpey, T. M., Van Hoeven, N., Carter, V. S., Thomas, M. J., Proll, S., Solorzano, A., Billharz, R., Fornek, J. L., Thomas, S., Chen, C.-H., Clark, E. A., Murali-Krishna, K., Katze, M. G. (2007). Functional Genomic and Serological Analysis of the Protective Immune Response Resulting from Vaccination of Macaques with an NS1-Truncated Influenza Virus. J. Virol. 81: 11817-11827 [Abstract] [Full Text]  
  • Ehrhardt, C., Wolff, T., Ludwig, S. (2007). Activation of Phosphatidylinositol 3-Kinase Signaling by the Nonstructural NS1 Protein Is Not Conserved among Type A and B Influenza Viruses. J. Virol. 81: 12097-12100 [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]  
  • Kochs, G., Garcia-Sastre, A., Martinez-Sobrido, L. (2007). Multiple Anti-Interferon Actions of the Influenza A Virus NS1 Protein. J. Virol. 81: 7011-7021 [Abstract] [Full Text]  
  • Roth-Cross, J. K., Martinez-Sobrido, L., Scott, E. P., Garcia-Sastre, A., Weiss, S. R. (2007). Inhibition of the Alpha/Beta Interferon Response by Mouse Hepatitis Virus at Multiple Levels. J. Virol. 81: 7189-7199 [Abstract] [Full Text]  
  • Melen, K., Kinnunen, L., Fagerlund, R., Ikonen, N., Twu, K. Y., Krug, R. M., Julkunen, I. (2007). Nuclear and Nucleolar Targeting of Influenza A Virus NS1 Protein: Striking Differences between Different Virus Subtypes. J. Virol. 81: 5995-6006 [Abstract] [Full Text]  
  • Yoneyama, M., Fujita, T. (2007). Function of RIG-I-like Receptors in Antiviral Innate Immunity. J. Biol. Chem. 282: 15315-15318 [Full Text]  
  • Kochs, G., Koerner, I., Thiel, L., Kothlow, S., Kaspers, B., Ruggli, N., Summerfield, A., Pavlovic, J., Stech, J., Staeheli, P. (2007). Properties of H7N7 influenza A virus strain SC35M lacking interferon antagonist NS1 in mice and chickens. J. Gen. Virol. 88: 1403-1409 [Abstract] [Full Text]  
  • Satterly, N., Tsai, P.-L., van Deursen, J., Nussenzveig, D. R., Wang, Y., Faria, P. A., Levay, A., Levy, D. E., Fontoura, B. M. A. (2007). Influenza virus targets the mRNA export machinery and the nuclear pore complex. Proc. Natl. Acad. Sci. USA 104: 1853-1858 [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»