Mammalian antiviral systems directed by small RNA

Abstract

There are strong incentives for human populations to develop antiviral systems. Similarly, genomes that encode antiviral systems have had strong selective advantages. Protein-guided immune systems, which have been well studied in mammals, are necessary for survival in our virus-laden environments. Small RNA–directed antiviral immune systems suppress invasion of cells by non-self genetic material via complementary base pairing with target sequences. These RNA silencing-dependent systems operate in diverse organisms. In mammals, there is strong evidence that microRNAs (miRNAs) regulate endogenous genes important for antiviral immunity, and emerging evidence that virus-derived nucleic acids can be directly targeted by small interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNAs (tRNAs) for protection in some contexts. In this review, we summarize current knowledge of the antiviral functions of each of these small RNA types and consider their conceptual and mechanistic overlap with innate and adaptive protein-guided immunity, including mammalian antiviral cytokines, as well as the prokaryotic RNA-guided immune system, CRISPR. In light of recent successes in delivery of RNA for antiviral purposes, most notably for vaccination, we discuss the potential for development of small noncoding RNA–directed antiviral therapeutics and prophylactics.

Altered microRNA expression in severe COVID‐19: Potential prognostic and pathophysiological role

“… 1 RNA silencing pathways have been identified as antiviral defense mechanisms in plants and insects, and possibly in mammalian cells. 2 To escape this antiviral defense, plant and insect viruses possess virus‐encoded suppressors of RNA interference, and this may extend to mammalian cells. 3 An interesting hypothesis to explain our findings is thus that SARS‐CoV‐2 targets cellular miRNA biogenesis.…”

Comparative transcriptomics reveals small RNA composition and differential microRNA responses underlying interferon-mediated antiviral regulation in porcine alveolar macrophages

“…Small RNAs (sRNAs) refer to a group of short (<200, and usually 18-30 nt in length) and non-coding RNA species. There are about seven families of sRNAs that mainly include microRNA (miRNA), small interfering RNA (siRNA), small nuclear RNA (SnRNA), small nucleolar RNA (snoRNA) and those derived from rRNA, tRNA, or fragments of transcribing genetic elements ( 14 , 15 ). Among them miRNAs and siRNA have been mainly studied for regulatory roles participating in various cellular processes, including RNA splicing, modification, degradation, and translational arrest.…”

“…Among them miRNAs and siRNA have been mainly studied for regulatory roles participating in various cellular processes, including RNA splicing, modification, degradation, and translational arrest. Small RNAs, especially miRNA are known to modulate the cell response to virus infections ( 14 , 15 ). Studies have provided evidence that miRNAs are pivotal in modulating macrophage polarization, differentiation, cytokine production, and inflammatory regulation ( 16 ).…”

Flavivirus Capsid Proteins Inhibit the Interferon Response

“…YFV and other flavivirus capsid proteins have been reported to suppress the RNA interference pathway by binding to dsRNA [ 31 ]. While the role of RNA interference in combatting viral infection in mammals has been controversial, more recent data suggest that it may indeed be an effective arm of the innate immune response (reviewed in [ 53 ]). In another study, DEAD box helicase 3 X-linked (DDX3X) was identified as a DENV capsid-binding protein [ 32 ].…”