title: Cigarette smoking products suppress anti-viral effects of Type I interferon via phosphorylation-dependent downregulation of its receptor.
abstract: While negative effect of smoking on the resistance to viral infections was known, the underlying mechanisms remained unclear. Here we report that products of cigarette smoking compromise the cellular anti-viral defenses by inhibiting the signaling induced by Type I interferon (IFN). Cigarette smoking condensate (but not pure nicotine) stimulated specific serine phosphorylation-dependent ubiquitination and degradation of the IFNAR1 subunit of the Type I IFN receptor leading to attenuation of IFN signaling and decreased resistance to viral infection. This resistance was restored in cells where phosphorylation-dependent degradation of IFNAR1 is abolished. We conclude that smoking compromises cellular anti-viral defenses via degradation of Type I IFN receptor and discuss the significance of this mechanism for efficacy of IFN-based therapies.
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Room 316, Hill Pavilion, 380 South University Avenue, Philadelphia, PA 19104-4539, USA.
authors: Wei-Chun
authors: WC
authors: HuangFu
authors: Jianghuai
authors: J
authors: Liu
authors: Ronald N
authors: RN
authors: Harty
authors: Serge Y
authors: SY
authors: Fuchs
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D053633:Receptor, Interferon alpha-beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012906:Smoke; D012907:Smoking / Q000276:immunology*; D018116:Vesiculovirus / Q000187:drug effects; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D012906:Smoke; D053633:Receptor, Interferon alpha-beta