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The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive‐strand RNA viruses
Author(s) -
Bonaventure Boris,
Rebendenne Antoine,
Chaves Valadão Ana Luiza,
ArnaudArnould Mary,
Gracias Ségolène,
Garcia de Gracia Francisco,
McKellar Joe,
Labaronne Emmanuel,
Tauziet Marine,
VivetBoudou Valérie,
Bernard Eric,
Briant Laurence,
Gros Nathalie,
Djilli Wassila,
Courgnaud Valérie,
Parrinello Hugues,
Rialle Stéphanie,
Blaise Mickaël,
Lacroix Laurent,
Lavigne Marc,
Paillart JeanChristophe,
Ricci Emiliano P,
Schulz Reiner,
Jouvenet Nolwenn,
Moncorgé Olivier,
Goujon Caroline
Publication year - 2022
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202154061
Subject(s) - rna , biology , rna helicase a , ribonucleoprotein , viral replication , rna silencing , transcription (linguistics) , rna dependent rna polymerase , helicase , virology , microbiology and biotechnology , virus , rna interference , genetics , gene , linguistics , philosophy
Genome‐wide screens are powerful approaches to unravel regulators of viral infections. Here, a CRISPR screen identifies the RNA helicase DDX42 as an intrinsic antiviral inhibitor of HIV‐1. Depletion of endogenous DDX42 increases HIV‐1 DNA accumulation and infection in cell lines and primary cells. DDX42 overexpression inhibits HIV‐1 infection, whereas expression of a dominant‐negative mutant increases infection. Importantly, DDX42 also restricts LINE‐1 retrotransposition and infection with other retroviruses and positive‐strand RNA viruses, including CHIKV and SARS‐CoV‐2. However, DDX42 does not impact the replication of several negative‐strand RNA viruses, arguing against an unspecific effect on target cells, which is confirmed by RNA‐seq analysis. Proximity ligation assays show DDX42 in the vicinity of viral elements, and cross‐linking RNA immunoprecipitation confirms a specific interaction of DDX42 with RNAs from sensitive viruses. Moreover, recombinant DDX42 inhibits HIV‐1 reverse transcription in vitro . Together, our data strongly suggest a direct mode of action of DDX42 on viral ribonucleoprotein complexes. Our results identify DDX42 as an intrinsic viral inhibitor, opening new perspectives to target the life cycle of numerous RNA viruses.