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

[Guest guest]

http://www.journals.uchicago.edu/doi/abs/10.1086/593216

The Journal of Infectious Diseases 2008;198:1766-1775

0022-1899/2008/19812-0007$15.00

DOI: 10.1086/593216

MAJOR ARTICLE

Alcohol Metabolism Increases the Replication of Hepatitis C Virus and Attenuates

the Antiviral Action of Interferon

M. McCartney,1,2

Ljiljana Semendric,1,2

Karla J. Helbig,1,2

Hinze,1,2

Brett ,3

A. Weinman,4 and

R. Beard1,2

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-á. 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-á 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.

Received 17 March 2008; accepted 17 July 2008; electronically published 28

October 2008.

Reprints or correspondence: Dr. R. Beard, School of Molecular and

Biomedical Science, The University of Adelaide, North Terrace, Adeleide, South

Australia, 5005, Australia (michael.beard@...).

Potential conflicts of interest: none reported.

Financial support: National Health & Medical Research Council of Australia

(NHMRC) (support to M.R.B., who is an NHMRC R. D. Research Fellow).

[Guest guest]

http://www.journals.uchicago.edu/doi/abs/10.1086/593216

The Journal of Infectious Diseases 2008;198:1766-1775

0022-1899/2008/19812-0007$15.00

DOI: 10.1086/593216

MAJOR ARTICLE

Alcohol Metabolism Increases the Replication of Hepatitis C Virus and Attenuates

the Antiviral Action of Interferon

M. McCartney,1,2

Ljiljana Semendric,1,2

Karla J. Helbig,1,2

Hinze,1,2

Brett ,3

A. Weinman,4 and

R. Beard1,2

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-á. 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-á 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.

Received 17 March 2008; accepted 17 July 2008; electronically published 28

October 2008.

Reprints or correspondence: Dr. R. Beard, School of Molecular and

Biomedical Science, The University of Adelaide, North Terrace, Adeleide, South

Australia, 5005, Australia (michael.beard@...).

Potential conflicts of interest: none reported.

Financial support: National Health & Medical Research Council of Australia

(NHMRC) (support to M.R.B., who is an NHMRC R. D. Research Fellow).