Discovery of Genes that Modulate Flavivirus Replication in an Interferon-Dependent Manner.
J Mol Biol ; 434(6): 167277, 2022 03 30.
Article in English | MEDLINE | ID: covidwho-2061566
ABSTRACTEstablishment of the interferon (IFN)-mediated antiviral state provides a crucial initial line of defense against viral infection. Numerous genes that contribute to this antiviral state remain to be identified. Using a loss-of-function strategy, we screened an original library of 1156 siRNAs targeting 386 individual curated human genes in stimulated microglial cells infected with Zika virus (ZIKV), an emerging RNA virus that belongs to the flavivirus genus. The screen recovered twenty-one potential host proteins that modulate ZIKV replication in an IFN-dependent manner, including the previously known IFITM3 and LY6E. Further characterization contributed to delineate the spectrum of action of these genes towards other pathogenic RNA viruses, including Hepatitis C virus and SARS-CoV-2. Our data revealed that APOL3 acts as a proviral factor for ZIKV and several other related and unrelated RNA viruses. In addition, we showed that MTA2, a chromatin remodeling factor, possesses potent flavivirus-specific antiviral functions induced by IFN. Our work identified previously unrecognized genes that modulate the replication of RNA viruses in an IFN-dependent manner, opening new perspectives to target weakness points in the life cycle of these viruses.
Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Replication / Interferons / Flavivirus Limits: Humans Language: English Journal: J Mol Biol Year: 2022 Document Type: Article Affiliation country: J.jmb.2021.167277