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Pré-Publication, Document De Travail Année : 2021

Discovery of genes that modulate flavivirus replication in an interferon-dependent manner

Sarah Lesage
  • Fonction : Auteur
Maxime Chazal
Guillaume Beauclair
Damien Batalie
  • Fonction : Auteur
Elodie Couderc
Aurianne Lescure
  • Fonction : Auteur
Elaine del Nery
Frédéric Tangy
Annette Martin
Nicolas Manel

Résumé

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. 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.

Dates et versions

hal-03448434 , version 1 (25-11-2021)

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Sarah Lesage, Maxime Chazal, Guillaume Beauclair, Damien Batalie, Elodie Couderc, et al.. Discovery of genes that modulate flavivirus replication in an interferon-dependent manner. 2021. ⟨hal-03448434⟩

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