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The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK
Immunology I Abstract 11
UPREGULATION OF THE TLR3 PATHWAY BY KSHV DURING PRIMARY INFECTION
OF MONOCYTES
John West, Sean Gregory and Blossom Damania
Department of Microbiology and Immunology and Lineberger Cancer Center, University of
North Carolina at Chapel Hill, North Carolina 27599
Abstract
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 on how KSHV infection modulates any TLR pathway. We
report the first evidence showing that KSHV upregulates TLR3 expression in human
monocytes sixteen hours post-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 IFN-β1 and CXCL10 (IP-10).
SiRNAs directed against TLR3 greatly reduced the ability of KSHV to upregulate IFN-β1
and CXCL10 upon infection. TLR3 upregulation was monitored at different time-points
post-infection. We found that TLR3 expression levels were highest 16 hours postinfection
and slowly declined thereafter returning to baseline by 120 hours post-infection
as the virus established latency.
Presenting author Email: john_west@med.unc.edu
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