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

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

doi:10.1016/j.febslet.2008.08.013

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Volume 582, Issue 21 , Pages 3206-3210, 22 September 2008

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

Edited by Gianni Cesareni

Wei-Chun HuangFu
- Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Room 316, Hill Pavilion, 380 South University Avenue, Philadelphia, PA 19104-4539, USA
- Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- These authors equally contributed to the manuscript.
Jianghuai Liu
- Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Room 316, Hill Pavilion, 380 South University Avenue, Philadelphia, PA 19104-4539, USA
- Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- These authors equally contributed to the manuscript.
Ronald N. Harty
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Serge Y. Fuchs
- Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Room 316, Hill Pavilion, 380 South University Avenue, Philadelphia, PA 19104-4539, USA
- Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Corresponding author. Address: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Room 316, Hill Pavilion, 380 South University Avenue, Philadelphia, PA 19104-4539, USA. Fax: +1 215 746 2295.

Received 4 August 2008; accepted 11 August 2008. published online 21 August 2008.

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.

Keywords: Interferon, Receptor, Ubiquitin, Smoking, Virus