Virus-derived siRNAs and piRNAs in immunity and pathogenesis

Cellular organisms have evolved related pathways for the biogenesis and function of small interfering RNAs (siRNAs), microRNAs and PIWI-interacting RNAs (piRNAs). These distinct classes of small RNAs guide specific gene silencing at both transcriptional and posttranscriptional levels by serving as specificity determinants. Small RNAs of virus and host origins have been found to modulate virus–host interactions by RNA interference (RNAi), leading to antiviral immunity or viral pathogenesis. Deep sequencing-based profiling of virus-derived small RNAs as products of host immune recognition not only allowed us to gain insight into the expansion and functional specialization of host factors involved in the antiviral immunity but also made it possible to identify new viruses in a culture-independent manner. Here we review recent developments on the characterization and function of virus-derived siRNAs and piRNAs in eukaryotic hosts.

► RNA-based immunity can terminate viral infection independently of Toll and Imd signaling in adult Drosophila. ► Virus-derived piRNAs are produced in fly and mosquito cells, suggesting an antiviral function for the piRNA pathway. ► Discovery of natural viral pathogens of C. elegans provides a new small animal model for immunity and pathogenesis studies. ► Viral disease symptoms can be induced by silencing of a host gene guided by a pathogen-derived siRNA. ► It remains unclear if the RNAi pathway has a natural antiviral role in mammals.