Upregulation of the TLR3 pathway by Kaposi's sarcoma-associated herpesvirus during primary infection.
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-beta1) and CXCL10 (IP-10). Small interfering RNAs directed against TLR3 greatly reduced the ability of KSHV to upregulate IFN-beta1 and CXCL10 upon infection.
West
John
J
Department of Microbiology and Immunology and Lineberger Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Damania
Blossom
B
D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; D034741:RNA, Small Interfering; D051196:Toll-Like Receptor 3