Viruses, microRNAs and RNA Interference

Abstract

In plants and invertebrates, RNA interference (RNAi) functions as a key innate immune response to viral infection. As a result, many plant viruses have evolved factors that can effectively inhibit RNAi and thereby facilitate virus replication. In contrast, efforts from several laboratories to identify an antiviral RNAi response in vertebrate cells infected by retro‐, flavi‐, or herpesviruses have so far failed to identify such a response, and artificial RNAi can be readily induced in virus infected human cells; i.e., viral infection of human cells does not result in a detectable inhibition of RNAi. In fact, rather than inhibiting RNAi, it is now clear that many DNA viruses encode microRNAs that are able to use the cellular RNAi machinery to inhibit the expression of cellular genes that have the potential to limit virus replication and/or that autoregulate viral gene expression. I will discuss our current understanding of the function of viral miRNAs and their potential contribution to viral pathogenesis, focusing on the identification of mRNA targets for the viral miRNAs encoded by the pathogenic human herpesviruses Herpes Simplex Virus 1 (HSV‐1) and Kaposi's Sarcoma‐associated Herpesvirus (KSHV).