title: A role for Ifit2 in restricting West Nile virus infection in the brain.
abstract: Previous studies have demonstrated that type I interferon (IFN-I) restricts West Nile virus (WNV) replication and pathogenesis in peripheral and central nervous system (CNS) tissues. However, the in vivo role of specific antiviral genes that are induced by IFN-I against WNV infection remains less well characterized. Here, using Ifit2(-/-) mice, we defined the antiviral function of the interferon-stimulated gene (ISG) Ifit2 in limiting infection and disease in vivo by a virulent North American strain of WNV. Compared to congenic wild-type controls, Ifit2(-/-) mice showed enhanced WNV infection in a tissue-restricted manner, with preferential replication in the CNS of animals lacking Ifit2. Virological analysis of cultured macrophages, dendritic cells, fibroblasts, cerebellar granule cell neurons, and cortical neurons revealed cell type-specific antiviral functions of Ifit2 against WNV. In comparison, small effects of Ifit2 were observed on the induction or magnitude of innate or adaptive immune responses. Our results suggest that Ifit2 restricts WNV infection and pathogenesis in different tissues in a cell type-specific manner.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Hyelim
authors.initials: H
authors.lastname: Cho
authors.forename: Bimmi
authors.initials: B
authors.lastname: Shrestha
authors.forename: Ganes C
authors.initials: GC
authors.lastname: Sen
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000276:immunology* / Q000821:virology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D014901:West Nile Fever / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014902:West Nile virus / Q000276:immunology*
chemical_list: D051017:Apoptosis Regulatory Proteins; C092572:Ifit2 protein, mouse; D011506:Proteins; D016601:RNA-Binding Proteins