Inhibition of flavivirus replication by a chromatin-remodeling factor – ViroChrom

The interferon response protects cells from invading viruses by inducing the expression of around 2,000 interferon-stimulated genes (ISGs). Only a handful of these ISGs have been well characterized. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting around 386 individual curated human ISGs (46% new). We have identified MTA2, a chromatin-remodeling factor, as a novel ISG that potently inhibits the replication of Zika virus, an emerging RNA virus belonging to the flavivirus genus. We propose to perform an in-depth characterization of the mode of action of MTA2 by using an innovative combination of virological and chromatin assays. Our work will increase our fundamental knowledge of antiviral response against members of the flavivirus genus. Furthermore, taking advantage of naturally occurring viral inhibitors, such as MTA2, may be an effective strategy for the development of novel drugs that activate, amplify or mimic their action.