Mechanisms of RNA Interference-Based Antiviral Strategies in Mammals

Abstract

Mammalian species possess sophisticated innate immune mechanisms that collectively combat a wide array of viral pathogens, with the interferon (IFN) response being extensively researched; however, the emerging role of antiviral RNAi in mammals is garnering significant interest, as evidenced by research indicating that Dicer, an enzyme essential for processing dsRNA, demonstrates reduced activity in vitro and that the IFN response may overshadow or inhibit the antiviral functions of RNAi in mammalian cells, raising questions about the functional relevance of RNAi in antiviral defense within mammalian somatic cells. This complexity is further illustrated by evidence suggesting a mutual inhibition between RNAi and the IFN pathway, where proteins like LGP2 inhibit Dicer, thus affecting the enzyme's capacity to process long dsRNA versus precursor miRNAs, potentially influencing antiviral efficacy. While traditional protein-guided immune responses are critical for survival in viral environments, small RNA-mediated antiviral systems utilizing complementary base pairing to silence non-self genetic material also play a crucial role, with emerging data indicating that miRNAs, siRNAs, piRNAs, and tRNAs can directly target virus-derived nucleic acids. This review aims to highlight some of the recent progress in understanding mammalian antiviral RNAi mechanisms.