RNA-based antiviral immunity

Abstract

RNA-based antiviral immunity is active in diverse host species, which produce virus-derived small RNAs in infected cells and use them as specificity determinants to guide specific virus clearance. Specific members of the Dicer family of proteins, which encode RNA helicase, double-stranded RNA (dsRNA)-binding and dsRNA-specific RNase domains, function as pattern recognition receptors (PRRs) in fungi, plants and invertebrates to detect viral dsRNA as a pathogen-associated molecular pattern (PAMP) and to further process it into virus-derived small interfering RNAs (siRNAs). Viral siRNAs are structurally similar to host endogenous siRNAs with monophosphate groups at the 5′ end and 2′-O-methyl groups at the 3′ end. They guide specific clearance of the invading viral RNAs by members of the Argonaute (AGO) protein family. Amplification of viral siRNAs by a host RNA-dependent RNA polymerase (RdRP) has an essential role in RNA-based antiviral immunity in plants. Distinct families of cellular RdRPs are conserved in all eukaryotes. Recent deep sequencing has identified siRNA-like virus-derived small RNAs in mammalian cells infected with distinct RNA viruses. However, it is not clear whether these viral small RNAs function in RNA-based viral immunity or other aspects of viral immunity and pathogenesis. Many nucleus-replicating DNA viruses that infect vertebrates and invertebrates encode up to 25 microRNAs (miRNAs) to regulate the expression of viral and host genes implicated in viral immunity and pathogenesis. The recent discovery of virus-derived Piwi-interacting RNAs (piRNAs) in infected Drosophila melanogaster cells, which are larger than the 21-nucleotide viral siRNAs, suggests that piRNAs might have a novel antiviral function in addition to their role in genome defence against transposons and repeat elements.