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 Google Scholar
Google Scholar
Right arrow Articles by Daffis, S.
Right arrow Articles by Diamond, M. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Daffis, S.
Right arrow Articles by Diamond, M. S.

 Previous Article  |  Next Article 

Journal of Virology, November 2008, p. 10349-10358, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00935-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Toll-Like Receptor 3 Has a Protective Role against West Nile Virus Infection{triangledown}

Stephane Daffis,1 Melanie A. Samuel,2 Mehul S. Suthar,4 Michael Gale Jr.,4 and Michael S. Diamond1,2,3*

Departments of Medicine,1 Molecular Microbiology,2 Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110,3 Department of Immunology, University of Washington School of Medicine, Seattle, Washington 98195-76504

Received 5 May 2008/ Accepted 13 August 2008

Protection against West Nile virus (WNV) infection requires rapid viral sensing and the generation of an interferon (IFN) response. Mice lacking IFN regulatory factor 3 (IRF-3) show increased vulnerability to WNV infection with enhanced viral replication and blunted IFN-stimulated gene (ISG) responses. IRF-3 functions downstream of several viral sensors, including Toll-like receptor 3 (TLR3), RIG-I, and MDA5. Cell culture studies suggest that host recognizes WNV in part, through the cytoplasmic helicase RIG-I and to a lesser extent, MDA5, both of which activate ISG expression through IRF-3. However, the role of TLR3 in vivo in recognizing viral RNA and activating antiviral defense pathways has remained controversial. We show here that an absence of TLR3 enhances WNV mortality in mice and increases viral burden in the brain. Compared to congenic wild-type controls, TLR3–/– mice showed relatively modest changes in peripheral viral loads. Consistent with this, little difference in multistep viral growth kinetics or IFN-{alpha}/β induction was observed between wild-type and TLR3–/– fibroblasts, macrophages, and dendritic cells. In contrast, a deficiency of TLR3 was associated with enhanced viral replication in primary cortical neuron cultures and greater WNV infection in central nervous system neurons after intracranial inoculation. Taken together, our data suggest that TLR3 serves a protective role against WNV in part, by restricting replication in neurons.

* Corresponding author. Mailing address: Departments of Medicine, Molecular Microbiology, and Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8051, St. Louis, MO 63110. Phone: (314) 362-2842. Fax: (314) 362-9230. E-mail: diamond{at}borcim.wustl.edu

{triangledown} Published ahead of print on 20 August 2008.

Journal of Virology, November 2008, p. 10349-10358, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00935-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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