Kaposiââ?¬â?¢s sarcoma-associated herpesvirus or Human herpesvirus-8 (KSHV/HHV-8),\nan oncogenic human herpesvirus and the leading cause of cancer in HIV-infected individuals, is a major\npublic health concern with recurring reports of epidemics on a global level. The early detection of\nKSHV virus and subsequent activation of the antiviral immune response by the hostââ?¬â?¢s immune system\nare crucial to prevent KSHV infection. The hostââ?¬â?¢s immune system is an evolutionary conserved\nsystem that provides the most important line of defense against invading microbial pathogens,\nincluding viruses. Viruses are initially detected by the cells of the host innate immune system,\nwhich evoke concerted antiviral responses via the secretion of interferons (IFNs) and inflammatory\ncytokines/chemokines for elimination of the invaders. Type I IFN and cytokine gene expression are\nregulated by multiple intracellular signaling pathways that are activated by germline-encoded host\nsensors, i.e., pattern recognition receptors (PRRs) that recognize a conserved set of ligands, known\nas ââ?¬Ë?pathogen-associated molecular patterns (PAMPs)ââ?¬â?¢. On the contrary, persistent and dysregulated\nsignaling of PRRs promotes numerous tumor-causing inflammatory events in various human cancers.\nBeing an integral component of the mammalian innate immune response and due to their constitutive\nactivation in tumor cells, targeting PRRs appears to be an effective strategy for tumor prevention\nand/or treatment. Cellular PRRs are known to respond to KSHV infection, and KSHV has been\nshown to be armed with an array of strategies to selectively inhibit cellular PRR-based immune\nsensing to its benefit. In particular, KSHV has acquired specific immunomodulatory genes to\neffectively subvert PRR responses during the early stages of primary infection, lytic reactivation and\nlatency, for a successful establishment of a life-long persistent infection. The current review aims to\ncomprehensively summarize the latest advances in our knowledge of role of PRRs in KSHV infections.
Loading....