title: The naturally attenuated Kunjin strain of West Nile virus shows enhanced sensitivity to the host type I interferon response.
abstract: The host determinants that contribute to attenuation of the naturally occurring nonpathogenic strain of West Nile virus (WNV), the Kunjin strain (WNV(KUN)), remain unknown. Here, we show that compared to a highly pathogenic North American strain, WNV(KUN) exhibited an enhanced sensitivity to the antiviral effects of type I interferon. Our studies establish that the virulence of WNV(KUN) can be restored in cells and mice deficient in specific interferon regulatory factors (IRFs) or the common type I interferon receptor. Thus, WNV(KUN) is attenuated primarily through its enhanced restriction by type I interferon- and IRF-3-dependent mechanisms.
authors.affiliation: Department of Medicine, Molecular Microbiology and Pathology & Immunology, Washington University School of Medicine, St. Louis. Missouri 63110, USA.
authors.forename: Stephane
authors.initials: S
authors.lastname: Daffis
authors.forename: Helen M
authors.initials: HM
authors.lastname: Lazear
authors.forename: Wen Jun
authors.initials: WJ
authors.lastname: Liu
authors.forename: Michelle
authors.initials: M
authors.lastname: Audsley
authors.forename: Michael
authors.initials: M
authors.lastname: Engle
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
authors.forename: Michael S
authors.initials: MS
authors.lastname: Diamond
mesh_terms: D000818:Animals; D002460:Cell Line; D002490:Central Nervous System / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D051379:Mice; D016019:Survival Analysis; D019562:Viral Load; D014774:Virulence; D014779:Virus Replication; D014901:West Nile Fever / Q000401:mortality / Q000821:virology; D014902:West Nile virus / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D007370:Interferon Type I