Cigarette smoking products suppress anti-viral effects of Type I interferon via phosphorylation-dependent downregulation of its receptor |
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Authors: | HuangFu Wei-Chun Liu Jianghuai Harty Ronald N Fuchs Serge Y |
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Affiliation: | Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Room 316, Hill Pavilion, 380 South University Avenue, Philadelphia, PA 19104-4539, USA. |
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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. |
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