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Type I IFN controls chikungunya virus via its action on nonhematopoietic cells

Chikungunya virus (CHIKV) is the causative agent of an outbreak that began in La Réunion in 2005 and remains a major public health concern in India, Southeast Asia, and southern Europe. CHIKV is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthra...

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Autores principales: Schilte, Clémentine, Couderc, Thérèse, Chretien, Fabrice, Sourisseau, Marion, Gangneux, Nicolas, Guivel-Benhassine, Florence, Kraxner, Anton, Tschopp, Jürg, Higgs, Stephen, Michault, Alain, Arenzana-Seisdedos, Fernando, Colonna, Marco, Peduto, Lucie, Schwartz, Olivier, Lecuit, Marc, Albert, Matthew L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822618/
https://www.ncbi.nlm.nih.gov/pubmed/20123960
http://dx.doi.org/10.1084/jem.20090851
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author Schilte, Clémentine
Couderc, Thérèse
Chretien, Fabrice
Sourisseau, Marion
Gangneux, Nicolas
Guivel-Benhassine, Florence
Kraxner, Anton
Tschopp, Jürg
Higgs, Stephen
Michault, Alain
Arenzana-Seisdedos, Fernando
Colonna, Marco
Peduto, Lucie
Schwartz, Olivier
Lecuit, Marc
Albert, Matthew L.
author_facet Schilte, Clémentine
Couderc, Thérèse
Chretien, Fabrice
Sourisseau, Marion
Gangneux, Nicolas
Guivel-Benhassine, Florence
Kraxner, Anton
Tschopp, Jürg
Higgs, Stephen
Michault, Alain
Arenzana-Seisdedos, Fernando
Colonna, Marco
Peduto, Lucie
Schwartz, Olivier
Lecuit, Marc
Albert, Matthew L.
author_sort Schilte, Clémentine
collection PubMed
description Chikungunya virus (CHIKV) is the causative agent of an outbreak that began in La Réunion in 2005 and remains a major public health concern in India, Southeast Asia, and southern Europe. CHIKV is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthralgia, and rash. As viral load in infected patients declines before the appearance of neutralizing antibodies, we studied the role of type I interferon (IFN) in CHIKV pathogenesis. Based on human studies and mouse experimentation, we show that CHIKV does not directly stimulate type I IFN production in immune cells. Instead, infected nonhematopoietic cells sense viral RNA in a Cardif-dependent manner and participate in the control of infection through their production of type I IFNs. Although the Cardif signaling pathway contributes to the immune response, we also find evidence for a MyD88-dependent sensor that is critical for preventing viral dissemination. Moreover, we demonstrate that IFN-α/β receptor (IFNAR) expression is required in the periphery but not on immune cells, as IFNAR(−/−)→WT bone marrow chimeras are capable of clearing the infection, whereas WT→IFNAR(−/−) chimeras succumb. This study defines an essential role for type I IFN, produced via cooperation between multiple host sensors and acting directly on nonhematopoietic cells, in the control of CHIKV.
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spelling pubmed-28226182010-08-15 Type I IFN controls chikungunya virus via its action on nonhematopoietic cells Schilte, Clémentine Couderc, Thérèse Chretien, Fabrice Sourisseau, Marion Gangneux, Nicolas Guivel-Benhassine, Florence Kraxner, Anton Tschopp, Jürg Higgs, Stephen Michault, Alain Arenzana-Seisdedos, Fernando Colonna, Marco Peduto, Lucie Schwartz, Olivier Lecuit, Marc Albert, Matthew L. J Exp Med Article Chikungunya virus (CHIKV) is the causative agent of an outbreak that began in La Réunion in 2005 and remains a major public health concern in India, Southeast Asia, and southern Europe. CHIKV is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthralgia, and rash. As viral load in infected patients declines before the appearance of neutralizing antibodies, we studied the role of type I interferon (IFN) in CHIKV pathogenesis. Based on human studies and mouse experimentation, we show that CHIKV does not directly stimulate type I IFN production in immune cells. Instead, infected nonhematopoietic cells sense viral RNA in a Cardif-dependent manner and participate in the control of infection through their production of type I IFNs. Although the Cardif signaling pathway contributes to the immune response, we also find evidence for a MyD88-dependent sensor that is critical for preventing viral dissemination. Moreover, we demonstrate that IFN-α/β receptor (IFNAR) expression is required in the periphery but not on immune cells, as IFNAR(−/−)→WT bone marrow chimeras are capable of clearing the infection, whereas WT→IFNAR(−/−) chimeras succumb. This study defines an essential role for type I IFN, produced via cooperation between multiple host sensors and acting directly on nonhematopoietic cells, in the control of CHIKV. The Rockefeller University Press 2010-02-15 /pmc/articles/PMC2822618/ /pubmed/20123960 http://dx.doi.org/10.1084/jem.20090851 Text en © 2010 Schilte et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Schilte, Clémentine
Couderc, Thérèse
Chretien, Fabrice
Sourisseau, Marion
Gangneux, Nicolas
Guivel-Benhassine, Florence
Kraxner, Anton
Tschopp, Jürg
Higgs, Stephen
Michault, Alain
Arenzana-Seisdedos, Fernando
Colonna, Marco
Peduto, Lucie
Schwartz, Olivier
Lecuit, Marc
Albert, Matthew L.
Type I IFN controls chikungunya virus via its action on nonhematopoietic cells
title Type I IFN controls chikungunya virus via its action on nonhematopoietic cells
title_full Type I IFN controls chikungunya virus via its action on nonhematopoietic cells
title_fullStr Type I IFN controls chikungunya virus via its action on nonhematopoietic cells
title_full_unstemmed Type I IFN controls chikungunya virus via its action on nonhematopoietic cells
title_short Type I IFN controls chikungunya virus via its action on nonhematopoietic cells
title_sort type i ifn controls chikungunya virus via its action on nonhematopoietic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822618/
https://www.ncbi.nlm.nih.gov/pubmed/20123960
http://dx.doi.org/10.1084/jem.20090851
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