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 Wilson, J. R.
Right arrow Articles by Scholle, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wilson, J. R.
Right arrow Articles by Scholle, F.

 Previous Article  |  Next Article 

Journal of Virology, September 2008, p. 8262-8271, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00226-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

West Nile Virus Nonstructural Protein 1 Inhibits TLR3 Signal Transduction {triangledown}

Jason R. Wilson, Paola Florez de Sessions, Megan A. Leon, and Frank Scholle*

Department of Microbiology, North Carolina State University, Raleigh, North Carolina 27695-7615

Received 1 February 2008/ Accepted 5 June 2008

The innate immune response is the first line of defense against foreign pathogens. The recognition of virus-associated molecular patterns, including double- and single-stranded RNA, by pattern recognition receptors initiates a cascade of signaling reactions. These result in the transcriptional upregulation and secretion of proinflammatory cytokines that induce an antiviral state. Many viruses have evolved mechanisms to antagonize these responses in order to help them establish a productive infection. We have previously shown that West Nile virus (WNV) is able to inhibit Toll-like receptor 3 (TLR3)-mediated activation of interferon (IFN) regulatory factor 3 (IRF3) (F. Scholle and P. W. Mason, Virology 342:77-87, 2005). In the present study, the WNV nonstructural (NS) proteins were analyzed individually for their ability to antagonize signal transduction mediated by TLR3. We report that expression of WNV NS1 inhibits TLR3-induced transcriptional activation of the IFN-β promoter and of an NF-{kappa}B-responsive promoter. This inhibition was due to a failure of the TLR3 ligand poly(I:C) to induce nuclear translocation of IRF3 and NF-{kappa}B. Furthermore, NS1 expression also inhibited TLR3-dependent production of interleukin-6 and the establishment of an antiviral state. The function of NS1 in flavivirus infection is not well understood. NS1 is required for viral RNA replication and is also secreted from mammalian cells but not from insect cells. Here, we identify a previously unrecognized role for NS1 in the modulation of signaling pathways of the innate immune response to WNV infection.

* Corresponding author. Mailing address: Department of Microbiology, CB7615, North Carolina State University, Raleigh, NC 27695-7615. Phone: (919) 513-7574. Fax: (919) 515-7867. E-mail: frank_scholle{at}ncsu.edu

{triangledown} Published ahead of print on 18 June 2008.

Journal of Virology, September 2008, p. 8262-8271, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00226-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  


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