Argonaute proteins and the mammalian antiviral response

RNA interference (RNAi) is a highly conserved system of gene silencing. Plants and insects use RNAi to suppress viruses, however the role of RNAi for mammalian antiviral defense is unclear. The studies proposed herein will characterize the mammalian RNAi components Argonautes1-4 during virus infection using the recently generated Argonaute deficient mice. In addition, deep sequencing of RNA bound to Argonautes in infected cells will uncover binding preferences of Argonautes towards viral and small RNA populations. Collectively, these findings will determine the role of Argonautes in antiviral defense and may lead to the development of more effective treatments for viral infection, including influenza, hepatitis C and HIV.