The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses

Boris Bonaventure; Antoine Rebendenne; Ana Luiza Chaves Valadão; Mary Arnaud-Arnould; Ségolène Gracias; Francisco Garcia de Gracia; Joe McKellar; Emmanuel Labaronne; Marine Tauziet; Valérie Vivet-Boudou; Eric Bernard; Laurence Briant; Nathalie Gros; Wassila Djilli; Valérie Courgnaud; Hugues Parrinello; Stéphanie Rialle; Mickaël Blaise; Laurent Lacroix; Marc Lavigne; Jean-Christophe Paillart; Emiliano P Ricci; Reiner Schulz; Nolwenn Jouvenet; Olivier Moncorgé; Caroline Goujon

doi:10.15252/embr.202154061

The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses

Boris Bonaventure, Antoine Rebendenne, Ana Luiza Chaves Valadão, Mary Arnaud-Arnould, Ségolène Gracias, Francisco Garcia de Gracia, Joe McKellar, Emmanuel Labaronne, Marine Tauziet, Valérie Vivet-Boudou, Eric Bernard, Laurence Briant, Nathalie Gros, Wassila Djilli, Valérie Courgnaud, Hugues Parrinello, Stéphanie Rialle, Mickaël Blaise, Laurent Lacroix, Marc LavigneJean-Christophe Paillart, Emiliano P Ricci, Reiner Schulz, Nolwenn Jouvenet, Olivier Moncorgé, Caroline Goujon

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

Abstract

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. [Abstract copyright: © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.]

Original language	English
Pages (from-to)	e54061
Journal	EMBO reports
Early online date	26 Sept 2022
DOIs	https://doi.org/10.15252/embr.202154061
Publication status	E-pub ahead of print - 26 Sept 2022

Keywords

DDX42 DEAD-box RNA helicase
RNA viruses
intrinsic immunity
viral inhibition

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.15252/embr.202154061Licence: CC BY

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Bonaventure, B., Rebendenne, A., Chaves Valadão, A. L., Arnaud-Arnould, M., Gracias, S., Garcia de Gracia, F., McKellar, J., Labaronne, E., Tauziet, M., Vivet-Boudou, V., Bernard, E., Briant, L., Gros, N., Djilli, W., Courgnaud, V., Parrinello, H., Rialle, S., Blaise, M., Lacroix, L., ... Goujon, C. (2022). The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses. EMBO reports, e54061. https://doi.org/10.15252/embr.202154061

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title = "The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses",

abstract = "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. [Abstract copyright: {\textcopyright} 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.]",

keywords = "DDX42 DEAD-box RNA helicase, RNA viruses, intrinsic immunity, viral inhibition",

author = "Boris Bonaventure and Antoine Rebendenne and {Chaves Valad{\~a}o}, {Ana Luiza} and Mary Arnaud-Arnould and S{\'e}gol{\`e}ne Gracias and {Garcia de Gracia}, Francisco and Joe McKellar and Emmanuel Labaronne and Marine Tauziet and Val{\'e}rie Vivet-Boudou and Eric Bernard and Laurence Briant and Nathalie Gros and Wassila Djilli and Val{\'e}rie Courgnaud and Hugues Parrinello and St{\'e}phanie Rialle and Micka{\"e}l Blaise and Laurent Lacroix and Marc Lavigne and Jean-Christophe Paillart and Ricci, {Emiliano P} and Reiner Schulz and Nolwenn Jouvenet and Olivier Moncorg{\'e} and Caroline Goujon",

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month = sep,

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Bonaventure, B, Rebendenne, A, Chaves Valadão, AL, Arnaud-Arnould, M, Gracias, S, Garcia de Gracia, F, McKellar, J, Labaronne, E, Tauziet, M, Vivet-Boudou, V, Bernard, E, Briant, L, Gros, N, Djilli, W, Courgnaud, V, Parrinello, H, Rialle, S, Blaise, M, Lacroix, L, Lavigne, M, Paillart, J-C, Ricci, EP, Schulz, R, Jouvenet, N, Moncorgé, O & Goujon, C 2022, 'The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses', EMBO reports, pp. e54061. https://doi.org/10.15252/embr.202154061

TY - JOUR

T1 - The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses

AU - Bonaventure, Boris

AU - Rebendenne, Antoine

AU - Chaves Valadão, Ana Luiza

AU - Arnaud-Arnould, Mary

AU - Gracias, Ségolène

AU - Garcia de Gracia, Francisco

AU - McKellar, Joe

AU - Labaronne, Emmanuel

AU - Tauziet, Marine

AU - Vivet-Boudou, Valérie

AU - Bernard, Eric

AU - Briant, Laurence

AU - Gros, Nathalie

AU - Djilli, Wassila

AU - Courgnaud, Valérie

AU - Parrinello, Hugues

AU - Rialle, Stéphanie

AU - Blaise, Mickaël

AU - Lacroix, Laurent

AU - Lavigne, Marc

AU - Paillart, Jean-Christophe

AU - Ricci, Emiliano P

AU - Schulz, Reiner

AU - Jouvenet, Nolwenn

AU - Moncorgé, Olivier

AU - Goujon, Caroline

PY - 2022/9/26

Y1 - 2022/9/26

N2 - 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. [Abstract copyright: © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.]

AB - 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. [Abstract copyright: © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.]

KW - DDX42 DEAD-box RNA helicase

KW - RNA viruses

KW - intrinsic immunity

KW - viral inhibition

U2 - 10.15252/embr.202154061

DO - 10.15252/embr.202154061

M3 - Article

C2 - 36161446

SN - 1469-3178

SP - e54061

JO - EMBO reports

JF - EMBO reports

ER -

The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses

Abstract

Keywords

UN SDGs

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