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Cancers 2018, 10(3), 85; https://doi.org/10.3390/cancers10030085

Role of Pattern Recognition Receptors in KSHV Infection

1
Department of Microbiology and Immunology, University of Nevada, Reno, School of Medicine, 1664 N, Virginia Street, MS 320, Reno, NV 89557, USA
2
Department of Internal Medicine, UTMB Galveston, League City Campus, 301 University Blvd, Galveston, TX 77555, USA
*
Author to whom correspondence should be addressed.
Received: 27 January 2018 / Revised: 12 March 2018 / Accepted: 16 March 2018 / Published: 20 March 2018
(This article belongs to the Special Issue Cancer Biomarkers)
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Abstract

Kaposi’s sarcoma-associated herpesvirus or Human herpesvirus-8 (KSHV/HHV-8), an oncogenic human herpesvirus and the leading cause of cancer in HIV-infected individuals, is a major public health concern with recurring reports of epidemics on a global level. The early detection of KSHV virus and subsequent activation of the antiviral immune response by the host’s immune system are crucial to prevent KSHV infection. The host’s immune system is an evolutionary conserved system that provides the most important line of defense against invading microbial pathogens, including viruses. Viruses are initially detected by the cells of the host innate immune system, which evoke concerted antiviral responses via the secretion of interferons (IFNs) and inflammatory cytokines/chemokines for elimination of the invaders. Type I IFN and cytokine gene expression are regulated by multiple intracellular signaling pathways that are activated by germline-encoded host sensors, i.e., pattern recognition receptors (PRRs) that recognize a conserved set of ligands, known as ‘pathogen-associated molecular patterns (PAMPs)’. On the contrary, persistent and dysregulated signaling of PRRs promotes numerous tumor-causing inflammatory events in various human cancers. Being an integral component of the mammalian innate immune response and due to their constitutive activation in tumor cells, targeting PRRs appears to be an effective strategy for tumor prevention and/or treatment. Cellular PRRs are known to respond to KSHV infection, and KSHV has been shown to be armed with an array of strategies to selectively inhibit cellular PRR-based immune sensing to its benefit. In particular, KSHV has acquired specific immunomodulatory genes to effectively subvert PRR responses during the early stages of primary infection, lytic reactivation and latency, for a successful establishment of a life-long persistent infection. The current review aims to comprehensively summarize the latest advances in our knowledge of role of PRRs in KSHV infections. View Full-Text
Keywords: innate immune responses; pattern recognition receptors; KSHV; interferons; cytokines; signaling pathways innate immune responses; pattern recognition receptors; KSHV; interferons; cytokines; signaling pathways
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Uppal, T.; Sarkar, R.; Dhelaria, R.; Verma, S.C. Role of Pattern Recognition Receptors in KSHV Infection. Cancers 2018, 10, 85.

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