Recent advances in the molecular biology of hepatitis C virus

Rosenberg, Steven

doi:10.1006/jmbi.2001.5055

Cited by 189 publications

(137 citation statements)

References 133 publications

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“…To directly link the action of alcohol with HCV expression, we used recently developed HCV replicon containing cell lines for this study. The establishment of the subgenomic replicon system represents major progress in the molecular biology of HCV replication, 21,27,41 which provides the first effective cellular system available for the study of the dynamics of virus replication. Although the HCV replicon system Huh.8 cells (3 ϫ 10 5 cells/2 mL/well) plated in a 6-well plate were transfected with pNF-B-Luc for 24 hours and then incubated with or without alcohol (100 mmol/L) and/or naltrexone (10 Ϫ8 mol/L) for 24 hours.…”

Section: Discussionmentioning

confidence: 99%

“…mimics only some aspects of HCV replication, this cell system provides an important means of investigating viral RNA and protein synthesis 21,27,41 and of characterizing those factor(s) that regulate HCV RNA expression. Using this system, we have for the first time shown that alcohol enhanced HCV replicon expression at both mRNA and protein levels (Figs.…”

Section: Discussionmentioning

confidence: 99%

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Alcohol Potentiates Hepatitis C Virus Replicon Expression

Zhang

Lai

et al. 2003

Hepatology

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H epatitis C virus (HCV) is responsible for the vast majority of cases of transfusion-associated and community-acquired non-A, non-B hepatitis 1,2 and infects an estimated 170 million people worldwide. 3 The seroprevalence of anti-HCV antibody in the United States has been estimated at 1.8%, which corresponds to approximately 4 million people. 4 HCV is the leading cause of chronic viral hepatitis in the United States, 5 and HCV-infected individuals are the major recipients of liver transplantation. HCV, first molecularly cloned in 1989, 1 is a positive-strand RNA virus of the flavivirus family with a genome size of ϳ10 kb, which encodes a number of structural (core, E1, E2, and p7) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A and NS5B) proteins. 6 HCV has at least 6 distinct but related genotypes with more than 50 subtypes, and genotype 1 is the most common in the United States, Europe, and most parts of Asia. HCV typically escapes clearance by the host's immune system and leads to the establishment of a persistent infection in approximately 70% of infected individuals. 7 The consequences of a subset of patients with chronic HCV infection are cirrhosis, liver failure, and hepatocellular carcinoma. 8,9 Treatment of HCV with interferon alfa (IFN-␣) and ribavirin is associated with a sustained response rate of less than 50%. 7,10,11 These limited therapeutic efficacies and the absence of an effective HCV vaccine underscore the importance of research on factors that enhance HCV infection and compromise IFN-␣-based therapy.Alcohol is the most commonly used and abused drug in the United States. Alcohol abuse significantly affects morbidity and mortality from infectious diseases. 12 Alcohol consumption accelerates liver damage, diminishes therapeutic response to IFN-␣, and increases the rate of hepatocellular carcinoma in patients with chronic HCV

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Alcohol Potentiates Hepatitis C Virus Replicon Expression

Zhang

Lai

et al. 2003

Hepatology

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“…38 Whereas these observations are compatible with antiviral activity of amantadine in HCV infection, the validity of the latter as an in vitro model for hepatic HCV infection has to be questioned. Because of the scarcity of in vitro models for HCV infection, 39 clinical trials remain the mainstay for determining efficacy of anti-HCV strategies.…”

Section: Discussionmentioning

confidence: 99%

Interferon and amantadine in naive chronic hepatitis C: A double-blind, randomized, placebo-controlled trial

Helbling

Stamenic

Viani³

et al. 2002

Hepatology

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Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment-naive patients with chronic hepatitis C yielded contradictory results. We therefore conducted a large, double-blind, placebo-controlled, multicenter trial in naive patients with chronic hepatitis C: 246 patients were randomized to receive interferon alfa-2a (6 MIU sc thrice weekly for 20 weeks, then 3 MIU sc thrice weekly) and either amantadine sulphate (2 ؋ 100 mg po QD) or placebo. Treatment continued for a total of 52 weeks, if HCV-RNA in serum polymerase chain reaction (PCR) had fallen below detection limit (1,000 copies/ mL) at treatment week 10, and stopped otherwise. All patients were followed for 24 weeks off therapy.

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“…The viral genome is 9.6 kb and encodes a single polyprotein, which is then processed by virally encoded and host enzymes into structural and nonstructural proteins. 2 Approximately seventy to eighty percent of patients develop persistent infection after acute exposure to HCV. 3 Viral load can be reduced and occasionally eliminated by interferon alfa (IFN-␣) treatment, either alone or in combination with the nucleoside analogue ribavirin.…”

mentioning

confidence: 99%