Cigarette smoking products suppress anti-viral effects of Type I interferon via phosphorylation-dependent downregulation of its receptor

Wei Chun HuangFu, Jianghuai Liu, Ronald N. Harty, Serge Y. Fuchs

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3206-3210
Number of pages5
JournalFEBS Letters
Volume582
Issue number21-22
DOIs
Publication statusPublished - Sep 22 2008
Externally publishedYes

Keywords

  • Interferon
  • Receptor
  • Smoking
  • Ubiquitin
  • Virus

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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