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 Fredericksen, B. L.
Right arrow Articles by Gale, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fredericksen, B. L.
Right arrow Articles by Gale, M., Jr.

 Previous Article  |  Next Article 

Journal of Virology, March 2006, p. 2913-2923, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2913-2923.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

West Nile Virus Evades Activation of Interferon Regulatory Factor 3 through RIG-I-Dependent and -Independent Pathways without Antagonizing Host Defense Signaling

Brenda L. Fredericksen and Michael Gale Jr.*

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas

Received 7 November 2005/ Accepted 1 January 2006

The ability of viruses to control and/or evade the host antiviral response is critical to the establishment of a productive infection. We have previously shown that West Nile virus NY (WNV-NY) delays activation of interferon regulatory factor 3 (IRF-3), a transcription factor critical to the initiation of the antiviral response. Here we demonstrate that the delayed activation of IRF-3 is essential for WNV-NY to achieve maximum virus production. Furthermore, WNV-NY utilizes a unique mechanism to control activation of IRF-3. In contrast to many other viruses that impose a nonspecific block to the IRF-3 pathway, WNV-NY eludes detection by the host cell at early times postinfection. To better understand this process, we assessed the role of the pathogen recognition receptor (PRR) retinoic acid-inducible gene I (RIG-I) in sensing WNV-NY infection. RIG-I null mouse embryo fibroblasts (MEFs) retained the ability to respond to WNV-NY infection; however, the onset of the host response was delayed compared to wild-type (WT) MEFs. This suggests that RIG-I is involved in initially sensing WNV-NY infection, while other PRRs sustain and/or amplify the host response later in infection. The delayed initiation of the host response correlated with an increase in WNV-NY replication in RIG-I null MEFs compared to WT MEFs. Our data suggest that activation of the host response by RIG-I early in infection is important for controlling replication of WNV-NY. Furthermore, pathogenic strains of WNV may have evolved to circumvent stimulation of the host response until after replication is well under way.

* Corresponding author. Mailing address: 5323 Harry Hines Blvd., Dallas, TX 75390-9048. Phone: (214) 648-5940. Fax: (214) 648-5905. E-mail: Michael.Gale{at}UTSouthwestern.edu.

Journal of Virology, March 2006, p. 2913-2923, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2913-2923.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Uzri, D., Gehrke, L. (2009). Nucleotide Sequences and Modifications That Determine RIG-I/RNA Binding and Signaling Activities. J. Virol. 83: 4174-4184 [Abstract] [Full Text]  
  • Daffis, S., Samuel, M. A., Suthar, M. S., Gale, M. Jr., Diamond, M. S. (2008). Toll-Like Receptor 3 Has a Protective Role against West Nile Virus Infection. J. Virol. 82: 10349-10358 [Abstract] [Full Text]  
  • Daffis, S., Samuel, M. A., Suthar, M. S., Keller, B. C., Gale, M. Jr., Diamond, M. S. (2008). Interferon Regulatory Factor IRF-7 Induces the Antiviral Alpha Interferon Response and Protects against Lethal West Nile Virus Infection. J. Virol. 82: 8465-8475 [Abstract] [Full Text]  
  • Wilson, J. R., de Sessions, P. F., Leon, M. A., Scholle, F. (2008). West Nile Virus Nonstructural Protein 1 Inhibits TLR3 Signal Transduction. J. Virol. 82: 8262-8271 [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]  
  • Silva, M. C., Guerrero-Plata, A., Gilfoy, F. D., Garofalo, R. P., Mason, P. W. (2007). Differential Activation of Human Monocyte-Derived and Plasmacytoid Dendritic Cells by West Nile Virus Generated in Different Host Cells. J. Virol. 81: 13640-13648 [Abstract] [Full Text]  
  • Arjona, A., Ledizet, M., Anthony, K., Bonafe, N., Modis, Y., Town, T., Fikrig, E. (2007). West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses. J. Immunol. 179: 8403-8409 [Abstract] [Full Text]  
  • Scherbik, S. V., Stockman, B. M., Brinton, M. A. (2007). Differential Expression of Interferon (IFN) Regulatory Factors and IFN-Stimulated Genes at Early Times after West Nile Virus Infection of Mouse Embryo Fibroblasts. J. Virol. 81: 12005-12018 [Abstract] [Full Text]  
  • Gilfoy, F. D., Mason, P. W. (2007). West Nile Virus-Induced Interferon Production Is Mediated by the Double-Stranded RNA-Dependent Protein Kinase PKR. J. Virol. 81: 11148-11158 [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]  
  • Liu, P., Jamaluddin, M., Li, K., Garofalo, R. P., Casola, A., Brasier, A. R. (2007). Retinoic Acid-Inducible Gene I Mediates Early Antiviral Response and Toll-Like Receptor 3 Expression in Respiratory Syncytial Virus-Infected Airway Epithelial Cells. J. Virol. 81: 1401-1411 [Abstract] [Full Text]  
  • Kinney, R. M., Huang, C. Y.-H., Whiteman, M. C., Bowen, R. A., Langevin, S. A., Miller, B. R., Brault, A. C. (2006). Avian virulence and thermostable replication of the North American strain of West Nile virus. J. Gen. Virol. 87: 3611-3622 [Abstract] [Full Text]  
  • Samuel, M. A., Diamond, M. S. (2006). Pathogenesis of West Nile Virus Infection: a Balance between Virulence, Innate and Adaptive Immunity, and Viral Evasion. J. Virol. 80: 9349-9360 [Full Text]  
  • Keller, B. C., Fredericksen, B. L., Samuel, M. A., Mock, R. E., Mason, P. W., Diamond, M. S., Gale, M. Jr. (2006). Resistance to Alpha/Beta Interferon Is a Determinant of West Nile Virus Replication Fitness and Virulence. J. Virol. 80: 9424-9434 [Abstract] [Full Text]  
  • Samuel, M. A., Whitby, K., Keller, B. C., Marri, A., Barchet, W., Williams, B. R. G., Silverman, R. H., Gale, M. Jr., Diamond, M. S. (2006). PKR and RNase L Contribute to Protection against Lethal West Nile Virus Infection by Controlling Early Viral Spread in the Periphery and Replication in Neurons. J. Virol. 80: 7009-7019 [Abstract] [Full Text]  
  • Gitlin, L., Barchet, W., Gilfillan, S., Cella, M., Beutler, B., Flavell, R. A., Diamond, M. S., Colonna, M. (2006). Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc. Natl. Acad. Sci. USA 103: 8459-8464 [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»