TY - JOUR
T1 - TLR-TRIF pathway enhances the expression of KSHV replication and transcription activator
AU - Meyer, Florencia
AU - Ehlers, Erica
AU - Steadman, Andrew
AU - Waterbury, Thomas
AU - Cao, Mingxia
AU - Zhang, Luwen
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/7/12
Y1 - 2013/7/12
N2 - Kaposi's sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus. KSHV replication and transcription activator (RTA) is necessary and sufficient for KSHV reactivation from latency. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, act through adaptors, and initiate innate and adaptiveimmuneresponses against pathogens. Toll/interleukin-1-receptor domain containing adaptor protein inducing interfer-on-β (TRIF) is an adaptor associated with TLR3 and TLR4 signaling, and is closely related to antiviral signaling to activate type I interferon (IFN) production. We previously found that KSHV RTA degrades TRIF indirectly and blocks TLR3 pathways. In this report, wefind that TRIF, as well as TLR3 activation, enhances KSHV RTA protein expression. The C-terminal region of the RTA is involved in the responding TRIF-mediated enhancement. The degradation of TRIF and the enhancement of RTA expression are using two different pathways. The enhancement by TLR-TRIF is at least partially via promoting translational efficiency of RTA mRNA. Finally, the receptor-interacting protein 1 (RIP1) may be involved in TRIF-mediated enhancement of RTA expression, but not in the RTA-mediated degradation of TRIF. Therefore, the activation of TLR-TRIF pathway enhances KSHV RTA protein expression, and KSHV RTA in turn degrades TRIF to block innate immunity. The putative KSHV-TLR-adaptor-interacting loopmaybea critical element to evade and usurp host innate immunity in KSHV life-cycle.
AB - Kaposi's sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus. KSHV replication and transcription activator (RTA) is necessary and sufficient for KSHV reactivation from latency. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, act through adaptors, and initiate innate and adaptiveimmuneresponses against pathogens. Toll/interleukin-1-receptor domain containing adaptor protein inducing interfer-on-β (TRIF) is an adaptor associated with TLR3 and TLR4 signaling, and is closely related to antiviral signaling to activate type I interferon (IFN) production. We previously found that KSHV RTA degrades TRIF indirectly and blocks TLR3 pathways. In this report, wefind that TRIF, as well as TLR3 activation, enhances KSHV RTA protein expression. The C-terminal region of the RTA is involved in the responding TRIF-mediated enhancement. The degradation of TRIF and the enhancement of RTA expression are using two different pathways. The enhancement by TLR-TRIF is at least partially via promoting translational efficiency of RTA mRNA. Finally, the receptor-interacting protein 1 (RIP1) may be involved in TRIF-mediated enhancement of RTA expression, but not in the RTA-mediated degradation of TRIF. Therefore, the activation of TLR-TRIF pathway enhances KSHV RTA protein expression, and KSHV RTA in turn degrades TRIF to block innate immunity. The putative KSHV-TLR-adaptor-interacting loopmaybea critical element to evade and usurp host innate immunity in KSHV life-cycle.
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U2 - 10.1074/jbc.M113.487421
DO - 10.1074/jbc.M113.487421
M3 - Article
C2 - 23723066
AN - SCOPUS:84880060940
VL - 288
SP - 20435
EP - 20442
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 28
ER -