Virus counterdefense: Diverse strategies for evading the RNA-silencing immunity

Viruses are obligate, intracellular pathogens that must manipulate and exploit host molecular mechanisms to prosper in the hostile cellular environment. Here we review the strategies used by viruses to evade the immunity controlled by 21- to 26-nt small RNAs. Viral suppressors of RNA silencing (VSRs) are encoded by genetically diverse viruses infecting plants, invertebrates, and vertebrates. VSRs target key steps in the small RNA pathways by inhibiting small RNA production, sequestering small RNAs, or preventing short- and long-distance spread of RNA silencing. However, although VSRs are required for infection, explicit data demonstrating a role of silencing suppression in virus infection are available only for a few VSRs. A subset of VSRs bind double-stranded RNA, but a distinct protein fold is revealed for each of the four VSRs examined. We propose that VSR families are evolved independently as a viral adaptation to immunity. Unresolved issues on the role of RNA silencing in virus-host interactions are highlighted.