RNA silencing is a small RNA based mechanism regulating gene expression and involved in many biological processes in most eukaryotes. In plants, nematodes and arthropods, this mechanism participates to antiviral defense. In mammals, although the RNA silencing machinery is present and needed for the microRNA pathway, its importance as an antiviral defense is still debated. In recent years, several studies have attempted to answer to the question of whether RNA silencing as an antiviral pathway is retained in mammals. However, these studies did not provide a clear answer yet. In this review, we will present the arguments for and against a relevant antiviral role of RNA interference (RNAi) in mammals, by discussing examples of active and functional mammalian antiviral RNAi in specific cell types and/or in specific conditions.
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