Alcohol Metabolism Increases the Replication of Hepatitis C Virus and Attenuates the Antiviral Action of Interferon

[Guest guest]

J Infect Dis. 2008 Oct 28. [Epub ahead of print]

Alcohol Metabolism Increases the Replication of Hepatitis C Virus and Attenuates

the Antiviral Action of Interferon.

McCartney EM, Semendric L, Helbig KJ, Hinze S, B, Weinman SA, Beard MR.

1Infectious Diseases Laboratories, Institute of Medical and Veterinary Science,

and 2School of Molecular and Biomedical Sciences, University of Adelaide, and

3Digestive Diseases Laboratory, Northern Clinical School, University of Sydney,

Sydney, Australia; 4Department of Neuroscience and Cell Biology, University of

Texas Medical Branch, Galveston.

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.

PMID: 18956976 [PubMed - as supplied by publisher]

[Guest guest]

J Infect Dis. 2008 Oct 28. [Epub ahead of print]

Alcohol Metabolism Increases the Replication of Hepatitis C Virus and Attenuates

the Antiviral Action of Interferon.

McCartney EM, Semendric L, Helbig KJ, Hinze S, B, Weinman SA, Beard MR.

1Infectious Diseases Laboratories, Institute of Medical and Veterinary Science,

and 2School of Molecular and Biomedical Sciences, University of Adelaide, and

3Digestive Diseases Laboratory, Northern Clinical School, University of Sydney,

Sydney, Australia; 4Department of Neuroscience and Cell Biology, University of

Texas Medical Branch, Galveston.

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.

PMID: 18956976 [PubMed - as supplied by publisher]