title: Cutting edge: independent roles for IRF-3 and IRF-7 in hematopoietic and nonhematopoietic cells during host response to Chikungunya infection.
abstract: The host response to Chikungunya virus is dependent on the direct action of type I IFN on infected nonhematopoietic cells. Prior studies have demonstrated that multiple host sensors coordinate an antiviral response; however, the tissue source(s) and signaling pathways for IFN production remain unknown. In this study, we demonstrate that IRF-3 and IRF-7 are functionally redundant, but lack of both factors results in lethal infection in adult mice. Reciprocal bone marrow chimeras indicated that IRF-3 or IRF-7 expression in either hematopoietic or nonhemotopoietic cell compartments was capable of inducing an antiviral response. Interestingly, redundancy of IRF-3 and IRF-7 was age dependent, as neonatal animals lacking either factor succumbed to infection. We further demonstrate that IPS-1 is essential in nonhematopoietic cells and preferentially required during early life. These results highlight the interplay between nonimmune and immune cells during Chikungunya virus infection and suggest an important role for nonhematopoietic cells as a critical source of IFN-α/β.
authors.affiliation: Unité d'Immunobiologie des Cellules Dendritiques, Département d'Immunologie, Institut Pasteur, Paris 75724, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Schilte
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Buckwalter
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Laird
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000367:Age Factors; D018354:Alphavirus Infections / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000254:growth & development / Q000276:immunology; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions; D050838:Interferon Regulatory Factor-3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050839:Interferon Regulatory Factor-7 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D011828:Radiation Chimera; D051199:Toll-Like Receptor 7 / Q000172:deficiency / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D051199:Toll-Like Receptor 7; C512612:MAVS protein, mouse; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; C507780:Myd88 protein, mouse; C477038:Tlr7 protein, mouse