1. Type I IFN controls chikungunya virus via its action on nonhematopoietic cells
- Author
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Stephen Higgs, Marco Colonna, Alain Michault, Fernando Arenzana-Seisdedos, Thérèse Couderc, Nicolas Gangneux, Marion Sourisseau, Matthew L. Albert, Anton Kraxner, Olivier Schwartz, Lucie Peduto, Fabrice Chrétien, Marc Lecuit, Florence Guivel-Benhassine, Jürg Tschopp, Clémentine Schilte, Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Microorganismes et Barrières de l'Hôte (Equipe avenir), Cellules Souches et Développement, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Virus et Immunité, Institute of Biochemistry, Université de Lausanne (UNIL)-BIL Biomedical Research Center, The University of Texas Medical Branch (UTMB), Service de microbiologie, Groupe Hospitalier Sud-CHR La réunion, Pathogénie Virale Moléculaire, Virologie, Centre National de la Recherche Scientifique (CNRS), Department of Immunology, Washington University, Développement des Tissus Lymphoïdes, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), This work was supported in part by grants from L'Agence Nationale de la Récherche and the Institut Pasteur Programmes Traversaux de Recherche (O. Schwartz, M. Lecuit, and M.L. Albert) and La Ligue Nationale Contre le Cancer, The EURYI Scheme, and European Science Foundation (M.L. Albert)., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL)-BIL Biomedical Research Center, Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Gau, Mireille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe avenir Microorganismes et Barrières de l'Hôte, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université de Lausanne ( UNIL ) -BIL Biomedical Research Center, The University of Texas Medical Branch ( UTMB ), Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Université Paris Descartes - Paris 5 ( UPD5 )
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Immunology ,Receptor, Interferon alpha-beta ,medicine.disease_cause ,Antibodies, Viral ,Virus ,Article ,03 medical and health sciences ,Mice ,Immune system ,Interferon ,[ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology ,Adaptor Proteins, Signal Transducing/immunology ,Adaptor Proteins, Signal Transducing/metabolism ,Alphavirus Infections/blood ,Alphavirus Infections/immunology ,Animals ,Antibodies, Neutralizing/blood ,Antibodies, Neutralizing/immunology ,Antibodies, Viral/blood ,Antibodies, Viral/immunology ,Blood Cells/immunology ,Blood Cells/metabolism ,Chikungunya virus ,Humans ,Interferon Type I/immunology ,Mice, Knockout ,RNA, Viral ,Receptor, Interferon alpha-beta/immunology ,Receptor, Interferon alpha-beta/metabolism ,Signal Transduction ,Viral Load ,medicine ,Immunology and Allergy ,Chikungunya ,Alphavirus infection ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,030304 developmental biology ,Adaptor Proteins, Signal Transducing ,0303 health sciences ,Blood Cells ,biology ,030306 microbiology ,Alphavirus Infections ,virus diseases ,medicine.disease ,Virology ,Antibodies, Neutralizing ,3. Good health ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,Interferon Type I ,biology.protein ,Antibody ,Viral load ,Interferon type I ,medicine.drug - Abstract
International audience; 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-alpha/beta 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.
- Published
- 2010
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