Alcohol metabolism increases the replication of hepatitis C virus and attenuates the antiviral action of interferon
Date
2008
Authors
McCartney, E.
Semendric, L.
Helbig, K.
Hinze, S.
Jones, B.
Weinman, S.
Beard, M.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Infectious Diseases, 2008; 198(12):1766-1775
Statement of Responsibility
Erin M. McCartney, Ljiljana Semendric, Karla J. Helbig, Susan Hinze, Brett Jones, Steven A. Weinman and Michael R. Beard
Conference Name
DOI
Abstract
The interactions between hepatitis C virus (HCV) and alcohol metabolism are not well understood. To determine the effect that alcohol metabolism has on HCV replication and the antiviral action of interferon (IFN), Huh-7 cells that harbor HCV replication and metabolize ethanol via the introduced expression of cytochrome P450 2E1 (Cyp2e1) were treated with ethanol and IFN-alpha. Treatment of these cells with ethanol (0-100 mmol/L) significantly increased HCV replication. This effect was dependent on Cyp2e1 expression and alcohol-metabolized oxidative stress (OS), because the antioxidant N-acetylcysteine blocked this effect. Furthermore, the anti-HCV action of IFN-alpha was attenuated in the presence of ethanol metabolism, most likely via attenuation of Stat1 tyrosine-701 phosphorylation. These in vitro results mimic what is often noted clinically, and further dissection of this model system will aid in our understanding of interactions between HCV and alcohol metabolism.