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Review
. 2016 Nov 30;39(11):777-782.
doi: 10.14348/molcells.2016.0232. Epub 2016 Nov 18.

Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV Evasion Strategies

Hye-Ra Lee  1 , Un Yung Choi  2 , Sung-Woo Hwang  1 , Stephanie Kim  2 , Jae U Jung  2
Affiliations
Review

Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV Evasion Strategies

Hye-Ra Lee et al. Mol Cells. .

Abstract

The innate immune system has evolved to detect and destroy invading pathogens before they can establish systemic infection. To successfully eradicate pathogens, including viruses, host innate immunity is activated through diverse pattern recognition receptors (PRRs) which detect conserved viral signatures and trigger the production of type I interferon (IFN) and pro-inflammatory cytokines to mediate viral clearance. Viral persistence requires that viruses co-opt cellular pathways and activities for their benefit. In particular, due to the potent antiviral activities of IFN and cytokines, viruses have developed various strategies to meticulously modulate intracellular innate immune sensing mechanisms to facilitate efficient viral replication and persistence. In this review, we highlight recent advances in the study of viral immune evasion strategies with a specific focus on how Kaposi's sarcoma-associated herpesvirus (KSHV) effectively targets host PRR signaling pathways.

Keywords: KSHV; PRRs; cytokines; immune evasion strategy; innate immune response; type I IFN.

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Figures

Fig. 1
Fig. 1
KSHV evasion of different recognition receptors signaling. Recognition of KSHV viral components by host pattern recognition receptors (PRR) triggers signaling pathways that induce production of type I IFN and pro-inflammatory cytokines. Following KSHV infection of cells, TLRs utilize MyD88 and TRIF as adaptor molecules to recruit downstream molecules, which eventually culminates in the production of type I IFN and/or pro-inflammatory cytokines. Moreover, KSHV dsDNA accumulates in the cytoplasm and is recognized by cGAS and IFI16. In response to DNA stimulation, STING, an ER protein, relocates to the cytoplasmic punctate structures and subsequently recruits TBK1 and IKKɛ. Alternatively, dsDNA is transcribed into dsRNA polymerase III in a cell-type specific manner and is recognized by RIG-I. RLRs signal through the adaptor protein MAVS located on the mitochondria triggers production of type I IFN together with NF-κB. Inflammasome induction by KSHV infection, either results in the activation of IL-1β and IL-18 or inhibition of its production due to blockage of the NLRP1/3. Red squares indicate KSHV proteins.
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