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Journal of Virology, June 2008, p. 5440-5449, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02590-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Upregulation of the TLR3 Pathway by Kaposi's Sarcoma-Associated Herpesvirus during Primary Infection{triangledown}

John West and Blossom Damania*

Department of Microbiology and Immunology and Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599

Received 5 December 2007/ Accepted 17 March 2008

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with several different human malignancies, including Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV establishes lifelong latency in the host and modulates the host immune response. Innate immunity is critical for controlling de novo viral infection. Toll-like receptors (TLRs) are key components of the innate immune system, and they serve as pathogen recognition receptors that stimulate the host antiviral response. In particular, TLR3 has been implicated in RNA virus recognition. Currently, there is no information regarding how KSHV infection modulates any TLR pathway. We report the first evidence that KSHV upregulates TLR3 expression in human monocytes during primary infection. This is also the first demonstration of a human DNA tumor virus upregulating TLR3, a TLR that thus far has been associated with the recognition of RNA viruses. We found that KSHV upregulates the TLR3 pathway and induces TLR3-specific cytokines and chemokines, including beta 1 interferon (IFN-β1) and CXCL10 (IP-10). Small interfering RNAs directed against TLR3 greatly reduced the ability of KSHV to upregulate IFN-β1 and CXCL10 upon infection.


* Corresponding author. Mailing address: Lineberger Comprehensive Cancer Center, CB 7295, University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 843-6011. Fax: (919) 966-9673. E-mail: damania{at}med.unc.edu

{triangledown} Published ahead of print on 26 March 2008.


Journal of Virology, June 2008, p. 5440-5449, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02590-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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