Viral RNA silencing suppressors (RSS): Novel strategy of viruses to ablate the host RNA interference (RNAi) defense system

Abstract

Pathogenic viruses have developed a molecular defense arsenal for their survival by counteracting the host anti-viral system known as RNA interference (RNAi). Cellular RNAi, in addition to regulating gene expression through microRNAs, also serves as a barrier against invasive foreign nucleic acids. RNAi is conserved across the biological species, including plants, animals and invertebrates. Viruses in turn, have evolved mechanisms that can counteract this anti-viral defense of the host. Recent studies of mammalian viruses exhibiting RNA silencing suppressor (RSS) activity have further advanced our understanding of RNAi in terms of host-virus interactions. Viral proteins and non-coding viral RNAs can inhibit the RNAi (miRNA/siRNA) pathway through different mechanisms. Mammalian viruses having dsRNA-binding regions and GW/WG motifs appear to have a high chance of conferring RSS activity. Although, RSSs of plant and invertebrate viruses have been well characterized, mammalian viral RSSs still need in-depth investigations to present the concrete evidences supporting their RNAi ablation characteristics. The information presented in this review together with any perspective research should help to predict and identify the RSS activity-endowed new viral proteins that could be the potential targets for designing novel anti-viral therapeutics.

HIV-1 RRE RNA acts as an RNA silencing suppressor by competing with TRBP-bound siRNAs

“…11,66,67 Many described proteins and RNAs acting as RSSs have mostly been shown to increase viral replication in cell lines from different origin than the natural host, although some have been shown in natural host cells. 68 In addition, the induction of RISC proteins upon virus entry has not been shown, pointing to an intrinsic mechanism rather than an inducible pathway. Among the RNAs shown to have RSS activity, adenovirus VA RNAs I and II and HIV-1 TAR have been characterized.…”

Single Cell Analysis of RNA-mediated Histone H3.3 Recruitment to a Cytomegalovirus Promoter-regulated Transcription Site

“…In invertebrates and plants, RNAi plays a significant role in heterochromatin regulation and is the primary defense against invasive foreign nucleic acids (85)(86)(87). In contrast, RNAi is thought to have regressed in mammals with the emergence of the interferon response and adaptive immunity, making it possible that its role in heterochromatin regulation also regressed (88).…”

MicroRNAs and HIV-1: Complex Interactions

“…In plants, RNAi serves as a host defense mechanism against viral infections (21,22). In mammals, the role of RNAi in regulating viral infection is less clear; however, accumulating findings are consistent with this role (23)(24)(25), including recent evidence that the virulence of viral infection in mammals is increased when host RNAi functions are attenuated (26 -30). Substantive advances have been made in our understanding of the interplay between HIV-1 and the cell's RNAi activity.…”