title: Type I IFN controls chikungunya virus via its action on nonhematopoietic cells.
abstract: 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.
authors.affiliation: Department of Immunology, Unité Immunobiologie des Cellules Dendritiques, Institut Pasteur, 75724 Paris, Cedex 15, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Schilte
authors.forename: Thérèse
authors.initials: T
authors.lastname: Couderc
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chretien
authors.forename: Marion
authors.initials: M
authors.lastname: Sourisseau
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gangneux
authors.forename: Florence
authors.initials: F
authors.lastname: Guivel-Benhassine
authors.forename: Anton
authors.initials: A
authors.lastname: Kraxner
authors.forename: Jürg
authors.initials: J
authors.lastname: Tschopp
authors.forename: Stephen
authors.initials: S
authors.lastname: Higgs
authors.forename: Alain
authors.initials: A
authors.lastname: Michault
authors.forename: Fernando
authors.initials: F
authors.lastname: Arenzana-Seisdedos
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Lucie
authors.initials: L
authors.lastname: Peduto
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: Marc
authors.initials: M
authors.lastname: Lecuit
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D018354:Alphavirus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001773:Blood Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002646:Chikungunya virus; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012367:RNA, Viral; D053633:Receptor, Interferon alpha-beta / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D019562:Viral Load
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007370:Interferon Type I; D012367:RNA, Viral; D053633:Receptor, Interferon alpha-beta