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Cigarette smoking products suppress anti‐viral effects of Type I interferon via phosphorylation‐dependent downregulation of its receptor
Author(s) -
HuangFu Wei-Chun,
Liu Jianghuai,
Harty Ronald N.,
Fuchs Serge Y.
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.08.013
Subject(s) - phosphorylation , downregulation and upregulation , receptor , interferon type i , interferon , signal transduction , biology , immunology , chemistry , microbiology and biotechnology , biochemistry , gene
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.