ArticleThe Journal of biological chemistry2010
Ethanol enhances hepatitis C virus replication through lipid metabolism and elevated NADH/NAD+.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
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Who cites it
28 citing papers in PubMed, 58 citations in OpenAlex.
- A Randomized Trial Comparing Brief Advice and Motivational Interviewing for Persons with HIV-HCV Co-infection Who Drink Alcohol.AIDS and behavior · 2021Trial
- Predictors and effects of alcohol use on liver function among young HCV-infected injection drug users in a behavioral intervention.Journal of hepatology · 2011Trial
- NADH elevation during chronic hypoxia leads to VHL-mediated HIF-1α degradation via SIRT1 inhibition.Cell & bioscience · 2023Article
- The Influence of Metabolic Factors in Patients with Chronic Viral Hepatitis C Who Received Oral Antiviral Treatment.Metabolites · 2023Article
- Effect of alcohol on clinical complications of hepatitis virus-induced liver cirrhosis: a consecutive ten-year study.BMC gastroenterology · 2022Article
- Second hits exacerbate alcohol-related organ damage: an update.Alcohol and alcoholism (Oxford, Oxfordshire) · 2021Review
- Disentangling the Progression of Non-alcoholic Fatty Liver Disease in the Human Gut Microbiota.Frontiers in microbiology · 2021Article
- Deciphering the co-adaptation of codon usage between respiratory coronaviruses and their human host uncovers candidate therapeutics for COVID-19.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Article
- Article
- Role of apoptotic hepatocytes in HCV dissemination: regulation by acetaldehyde.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- Hepatic steatosis in HCV-infected persons in the direct-acting antiviral era.Tropical diseases, travel medicine and vaccines · 2016Review
- Article
- Hepatitis C, innate immunity and alcohol: friends or foes?Biomolecules · 2015Review
- Impact of Alcohol Abuse on the Adaptive Immune System.Alcohol research : current reviews · 2015Review
- Update on Alcohol and Viral Hepatitis.Journal of clinical and translational hepatology · 2014Review
- Establishment of chronic hepatitis C virus infection: translational evasion of oxidative defence.World journal of gastroenterology · 2014Review
- Prominent steatosis with hypermetabolism of the cell line permissive for years of infection with hepatitis C virus.PloS one · 2014Article
- Hepatitis C and alcohol exacerbate liver injury by suppression of FOXO3.The American journal of pathology · 2013Article
- Predictors of alcohol use among rural drug users after disclosure of hepatitis C virus status.Journal of studies on alcohol and drugs · 2013Article
- Alcohol facilitates HCV RNA replication via up-regulation of miR-122 expression and inhibition of cyclin G1 in human hepatoma cells.Alcoholism, clinical and experimental research · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledEthanol has been suggested to elevate HCV titer in patients and to increase HCV RNA in replicon cells, suggesting that HCV replication is increased in the presence and absence of the complete viral replication cycle, but the mechanisms remain unclear. In this study, we use Huh7 human hepatoma cells that naturally express comparable levels of CYP2E1 as human liver to demonstrate that ethanol, at subtoxic and physiologically relevant concentrations, enhances complete HCV replication. The viral RNA genome replication is affected for both genotypes 2a and 1b. Acetaldehyde, a major product of ethanol metabolism, likewise enhances HCV replication at physiological concentrations. The potentiation of HCV replication by ethanol is suppressed by inhibiting CYP2E1 or aldehyde dehydrogenase and requires an elevated NADH/NAD(+) ratio. In addition, acetate, isopropyl alcohol, and concentrations of acetone that occur in diabetics enhance HCV replication with corresponding increases in the NADH/NAD(+). Furthermore, inhibiting the host mevalonate pathway with lovastatin or fluvastatin and fatty acid synthesis with 5-(tetradecyloxy)-2-furoic acid or cerulenin significantly attenuates the enhancement of HCV replication by ethanol, acetaldehyde, acetone, as well as acetate, whereas inhibiting beta-oxidation with beta-mercaptopropionic acid increases HCV replication. Ethanol, acetaldehyde, acetone, and acetate increase the total intracellular cholesterol content, which is attenuated with lovastatin. In contrast, both endogenous and exogenous ROS suppress the replication of HCV genotype 2a, as previously shown with genotype 1b.
conclusionTherefore, lipid metabolism and alteration of cellular NADH/NAD(+) ratio are likely to play a critical role in the potentiation of HCV replication by ethanol rather than oxidative stress.
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Registered trials
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