Innate Immune Recognition During RNA Virus Infection: Molecular Mechanisms —A Review

Abstract

     RNA viruses continue to pose a risk for human and animal health because they mutate at high rates and can enact measures of evasive action against host immune defenses. Innate immune system, which is responsible for sensing of viral RNA via PRR such as TLRs (Toll-like receptors), RLRs (RIG-I-like receptors) and NLRs (NOD-like receptors), to mount rapid interferon and pro-inflammatory responses thus act as the first line of antiviral defense. The integrated antiviral response is directed through distinct biological components manifested in mitochondrial antiviral signaling proteins (MAVS), transcription factors NF-κB and IRF3/7, and inflammasome complexes. However, RNA viruses have evolved various means of evading these innate defense mechanisms, by: (1) targeting and cleaving mitochondrial antiviral signaling proteins (MAVS); (2) preventing the addition of ubiquitin to the relevant signaling molecules; and (3) preventing the production of interferon alpha/beta [9]. The introduction of classes of sensors, such as ZBP1-mediated PANoptosis, DHX helicases and the cGAS-STING pathways represent novel antiviral recognition mechanisms that open new therapeutic avenues. In this review we detail classical and contemporary observations of innate immune recognition, highlight mechanisms viruss have developed to counteract host defenses, delineate how vaccine adjuvants may bypass these viral antagonism strategies and sketch implications for the development of therapeutics against important human viruses. Accordingly, deciphering these complex host-

pathogen interactions has major implications for the design of direct antiviral therapeutics and alternative indirect immunomodulatory strategies.