The interferon (IFN) response is a critical arm of the innate immune response and a major host defence mechanism against viral infections. Numerous genes that contribute to this antiviral state remain to be identified and characterized. Using large-scale loss-of-function strategies, we screened siRNAs or gRNAs libraries targeting hundreds of IFN-stimulated genes (ISGs) in IFN-treated cells infected with human RNA viruses, including SARS-CoV-2, Zika virus or tick-borne encephalitis virus. We recovered previously-unrecognized human genes able to modulate the replication of these RNA viruses in an IFN-dependent manner. For instance, we identified the chromatin remodelling protein MTA2 as a potent flavivirus-specific antiviral factor. Mechanistic studies to decipher the molecular mechanisms by which these novel antiviral genes are functioning are ongoing. We are also expanding our studies to the identification and characterization of ISGs in animal species that serve as viral reservoirs, such as bats. Our studies should open new perspectives to target weakness points in the life cycle of these emerging RNA viruses.
Published on January 17, 2022