title: The interferon-inducible gene viperin restricts West Nile virus pathogenesis.
abstract: Type I interferon (IFN) signaling coordinates an early antiviral program in infected and uninfected cells by inducing IFN-stimulated genes (ISGs) that modulate viral entry, replication, and assembly. However, the specific antiviral functions in vivo of most ISGs remain unknown. Here, we examined the contribution of the ISG viperin to the control of West Nile virus (WNV) in genetically deficient cells and mice. While modest increases in levels of WNV replication were observed for primary viperin(-/-) macrophages and dendritic cells, no appreciable differences were detected in deficient embryonic cortical neurons or fibroblasts. In comparison, viperin(-/-) adult mice infected with WNV via the subcutaneous or intracranial route showed increased lethality and/or enhanced viral replication in central nervous system (CNS) tissues. In the CNS, viperin expression was induced in both WNV-infected and adjacent uninfected cells, including activated leukocytes at the site of infection. Our experiments suggest that viperin restricts the infection of WNV in a tissue- and cell-type-specific manner and may be an important ISG for controlling viral infections that cause CNS disease.
authors: Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8051, St. Louis, MO 63110, USA.
authors: Kristy J
authors: KJ
authors: Szretter
authors: James D
authors: JD
authors: Brien
authors: Larissa B
authors: LB
authors: Thackray
authors: Herbert W
authors: HW
authors: Virgin
authors: Peter
authors: P
authors: Cresswell
authors: Michael S
authors: MS
authors: Diamond
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000821:virology; D003713:Dendritic Cells / Q000821:virology; D005347:Fibroblasts / Q000821:virology; D007372:Interferons / Q000276:immunology*; D008264:Macrophages / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000821:virology; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D014902:West Nile virus / Q000276:immunology* / Q000472:pathogenicity*; D000090123:Viperin Protein
chemical_list: D007372:Interferons; D011506:Proteins; C417529:Rsad2 protein, mouse; D000090123:Viperin Protein