RNAi-mediated antiviral immunity in mammals

RNA interference (RNAi) was discovered in plants where it functions as the main antiviral pathway and this antiviral role was subsequently extended to invertebrates. But it remained hotly debated whether RNAi fulfils a similar role in mammals that already have a potent innate immune system based on interferon and an elaborate adaptive immune system. On the one hand, mammalian cells do encode most of the RNAi machinery, but this could be used exclusively to control cellular gene expression via micro RNAs (miRNAs). But on the other hand, virus-derived small interfering RNAs, the hallmark of RNAi involvement, could not be readily detected upon virus infection of mammalian cells. However, recent studies have indicated that these signature molecules are generated in virus-infected embryonic cell types of mammals and that viruses actively suppress such responses by means of potent RNAi suppressor proteins. Thus, the tide seems to be changing in favor of RNAi as accessory antiviral defense mechanism in humans. Intriguingly, recent studies indicate that insects have also developed an additional innate immune system that collaborates with the RNAi response in the fight against invading viral pathogens. Thus, the presence of multiple antiviral response mechanisms seems standard outside the plant world and we will specifically discuss the interactions between these antiviral programs.