Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.

Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent prot...

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Autores principales:	Giovanna Clavarino, Nuno Cláudio, Thérèse Couderc, Alexandre Dalet, Delphine Judith, Voahirana Camosseto, Enrico K Schmidt, Till Wenger, Marc Lecuit, Evelina Gatti, Philippe Pierre
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0ef2a22482c8471a8af2d1447ac0357f
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spelling	oai:doaj.org-article:0ef2a22482c8471a8af2d1447ac0357f2021-11-18T06:04:24ZInduction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.1553-73661553-737410.1371/journal.ppat.1002708https://doaj.org/article/0ef2a22482c8471a8af2d1447ac0357f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22615568/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection.Giovanna ClavarinoNuno CláudioThérèse CoudercAlexandre DaletDelphine JudithVoahirana CamossetoEnrico K SchmidtTill WengerMarc LecuitEvelina GattiPhilippe PierrePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 5, p e1002708 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Giovanna Clavarino Nuno Cláudio Thérèse Couderc Alexandre Dalet Delphine Judith Voahirana Camosseto Enrico K Schmidt Till Wenger Marc Lecuit Evelina Gatti Philippe Pierre Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.
description	Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection.
format	article
author	Giovanna Clavarino Nuno Cláudio Thérèse Couderc Alexandre Dalet Delphine Judith Voahirana Camosseto Enrico K Schmidt Till Wenger Marc Lecuit Evelina Gatti Philippe Pierre
author_facet	Giovanna Clavarino Nuno Cláudio Thérèse Couderc Alexandre Dalet Delphine Judith Voahirana Camosseto Enrico K Schmidt Till Wenger Marc Lecuit Evelina Gatti Philippe Pierre
author_sort	Giovanna Clavarino
title	Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.
title_short	Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.
title_full	Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.
title_fullStr	Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.
title_full_unstemmed	Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.
title_sort	induction of gadd34 is necessary for dsrna-dependent interferon-β production and participates in the control of chikungunya virus infection.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0ef2a22482c8471a8af2d1447ac0357f
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Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.

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