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ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity

BACKGROUND: The role of innate immunity in general and of type I interferon (IFN-I) in particular in HTLV-1 pathogenesis is still a matter of debate. ADAR1-p150 is an Interferon Stimulated Gene (ISG) induced by IFN-I that can edit viral RNAs. We therefore investigated whether it could play the role...

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Autores principales: Cachat, Anne, Alais, Sandrine, Chevalier, Sébastien Alain, Journo, Chloé, Fusil, Floriane, Dutartre, Hélène, Boniface, Adrien, Ko, Nga Ling, Gessain, Antoine, Cosset, François-Loïc, Suspène, Rodolphe, Vartanian, Jean-Pierre, Mahieux, Renaud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245799/
https://www.ncbi.nlm.nih.gov/pubmed/25389016
http://dx.doi.org/10.1186/s12977-014-0093-9
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author Cachat, Anne
Alais, Sandrine
Chevalier, Sébastien Alain
Journo, Chloé
Fusil, Floriane
Dutartre, Hélène
Boniface, Adrien
Ko, Nga Ling
Gessain, Antoine
Cosset, François-Loïc
Suspène, Rodolphe
Vartanian, Jean-Pierre
Mahieux, Renaud
author_facet Cachat, Anne
Alais, Sandrine
Chevalier, Sébastien Alain
Journo, Chloé
Fusil, Floriane
Dutartre, Hélène
Boniface, Adrien
Ko, Nga Ling
Gessain, Antoine
Cosset, François-Loïc
Suspène, Rodolphe
Vartanian, Jean-Pierre
Mahieux, Renaud
author_sort Cachat, Anne
collection PubMed
description BACKGROUND: The role of innate immunity in general and of type I interferon (IFN-I) in particular in HTLV-1 pathogenesis is still a matter of debate. ADAR1-p150 is an Interferon Stimulated Gene (ISG) induced by IFN-I that can edit viral RNAs. We therefore investigated whether it could play the role of an anti-HTLV factor. RESULTS: We demonstrate here that ADAR1 is also expressed in the absence of IFN stimulation in activated primary T-lymphocytes that are the natural target of this virus and in HTLV-1 or HTLV-2 chronically infected T-cells. ADAR1 expression is also increased in primary lymphocytes obtained from HTLV-1 infected individuals. We show that ADAR1 enhances HTLV-1 and HTLV-2 infection in T-lymphocytes and that this proviral effect is independent from its editing activity. ADAR1 expression suppresses IFN-α inhibitory effect on HTLV-1 and HTLV-2 and acts through the repression of PKR phosphorylation. DISCUSSION: This study demonstrates that two interferon stimulated genes, i.e. PKR and ADAR1 have opposite effects on HTLV replication in vivo. The balanced expression of those proteins could determine the fate of the viral cycle in the course of infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0093-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-42457992014-11-28 ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity Cachat, Anne Alais, Sandrine Chevalier, Sébastien Alain Journo, Chloé Fusil, Floriane Dutartre, Hélène Boniface, Adrien Ko, Nga Ling Gessain, Antoine Cosset, François-Loïc Suspène, Rodolphe Vartanian, Jean-Pierre Mahieux, Renaud Retrovirology Research BACKGROUND: The role of innate immunity in general and of type I interferon (IFN-I) in particular in HTLV-1 pathogenesis is still a matter of debate. ADAR1-p150 is an Interferon Stimulated Gene (ISG) induced by IFN-I that can edit viral RNAs. We therefore investigated whether it could play the role of an anti-HTLV factor. RESULTS: We demonstrate here that ADAR1 is also expressed in the absence of IFN stimulation in activated primary T-lymphocytes that are the natural target of this virus and in HTLV-1 or HTLV-2 chronically infected T-cells. ADAR1 expression is also increased in primary lymphocytes obtained from HTLV-1 infected individuals. We show that ADAR1 enhances HTLV-1 and HTLV-2 infection in T-lymphocytes and that this proviral effect is independent from its editing activity. ADAR1 expression suppresses IFN-α inhibitory effect on HTLV-1 and HTLV-2 and acts through the repression of PKR phosphorylation. DISCUSSION: This study demonstrates that two interferon stimulated genes, i.e. PKR and ADAR1 have opposite effects on HTLV replication in vivo. The balanced expression of those proteins could determine the fate of the viral cycle in the course of infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-014-0093-9) contains supplementary material, which is available to authorized users. BioMed Central 2014-11-12 /pmc/articles/PMC4245799/ /pubmed/25389016 http://dx.doi.org/10.1186/s12977-014-0093-9 Text en © Cachat et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Cachat, Anne
Alais, Sandrine
Chevalier, Sébastien Alain
Journo, Chloé
Fusil, Floriane
Dutartre, Hélène
Boniface, Adrien
Ko, Nga Ling
Gessain, Antoine
Cosset, François-Loïc
Suspène, Rodolphe
Vartanian, Jean-Pierre
Mahieux, Renaud
ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity
title ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity
title_full ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity
title_fullStr ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity
title_full_unstemmed ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity
title_short ADAR1 enhances HTLV-1 and HTLV-2 replication through inhibition of PKR activity
title_sort adar1 enhances htlv-1 and htlv-2 replication through inhibition of pkr activity
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245799/
https://www.ncbi.nlm.nih.gov/pubmed/25389016
http://dx.doi.org/10.1186/s12977-014-0093-9
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