Discovery of genes that modulate flavivirus replication in an interferon-dependent manner
Virologie
; 26(2):120, 2022.
Article
in English
| EMBASE | ID: covidwho-1912931
ABSTRACT
Establishment 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. We are currently investigating the molecular mechanisms behind IFN-dependent flaviviral restriction of MTA2. Our work identified previously unrecognized genes that modulate the replication of RNA viruses in an IFN-dependent way, opening new perspectives to target weakness points in the life cycle of these viruses.
antivirus agent; endogenous compound; interferon; small interfering RNA; chromatin assembly and disassembly; conference abstract; controlled study; Flavivirus; Hepatitis C virus; human; human cell; human experiment; life cycle; loss of function mutation; microglia; nonhuman; protein function; RNA virus; Severe acute respiratory syndrome coronavirus 2; weakness; Zika virus
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Virologie
Year:
2022
Document Type:
Article
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