Life style-related diseases of the digestive system: Cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: Suppression of HCV replication by statins and synergistic action with interferon

Masanori Ikeda, Nobuyuki Kato

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) infection causes chronic hepatitis and leads to liver fibrosis and hepatocellular carcinoma. Pegylated-interferon and ribavirin is the current standard therapy for chronic hepatitis C. However, the therapy is only effective in 50% of the patients. To overcome this problem, we recently developed the HCV cell culture system (OR6 system) for the screening of anti-HCV reagents. In this OR6 system, the luciferase gene was introduced into the upstream portion of the HCV genome to facilitate the monitoring of HCV RNA replication. Recently lipid metabolism is reported to be involved in HCV RNA replication. Cholesterol and sphingolipid are the major components in lipid rafts, which seem to be the scaffold for HCV RNA replication. Statins inhibit cholesterol biosynthesis and also have the pleiotropic effects by the inhibition of prenylation. We demonstrated different anti-HCV effects of statins (atorvastatin, simvastatin, fluvastatin, lovastatin, and pitavastatin) using the OR6 system. Surprisingly, in contrast to the other statins, pravastatin exhibited no anti-HCV effect. Furthermore, statins enhanced the anti-HCV effect of interferon in combination. Statins may be a promising candidate for the adjuvant in interferon therapy and may improve the efficiency of the current interferon and ribavirin therapy.

Original languageEnglish
Pages (from-to)145-150
Number of pages6
JournalJournal of Pharmacological Sciences
Volume105
Issue number2
DOIs
Publication statusPublished - 2007

Fingerprint

Digestive System Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Virus Replication
Hepacivirus
Interferons
Life Style
Cell Culture Techniques
fluvastatin
Ribavirin
RNA
Cholesterol
Prenylation
Pravastatin
Lovastatin
Sphingolipids
Simvastatin
Chronic Hepatitis C
Virus Diseases
Chronic Hepatitis
Therapeutics

Keywords

  • Cell culture system
  • Hepatitis C virus (HCV)
  • Interferon
  • Life style-related disease
  • Statin

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Life style-related diseases of the digestive system: Cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: Suppression of HCV replication by statins and synergistic action with interferon",
abstract = "Hepatitis C virus (HCV) infection causes chronic hepatitis and leads to liver fibrosis and hepatocellular carcinoma. Pegylated-interferon and ribavirin is the current standard therapy for chronic hepatitis C. However, the therapy is only effective in 50{\%} of the patients. To overcome this problem, we recently developed the HCV cell culture system (OR6 system) for the screening of anti-HCV reagents. In this OR6 system, the luciferase gene was introduced into the upstream portion of the HCV genome to facilitate the monitoring of HCV RNA replication. Recently lipid metabolism is reported to be involved in HCV RNA replication. Cholesterol and sphingolipid are the major components in lipid rafts, which seem to be the scaffold for HCV RNA replication. Statins inhibit cholesterol biosynthesis and also have the pleiotropic effects by the inhibition of prenylation. We demonstrated different anti-HCV effects of statins (atorvastatin, simvastatin, fluvastatin, lovastatin, and pitavastatin) using the OR6 system. Surprisingly, in contrast to the other statins, pravastatin exhibited no anti-HCV effect. Furthermore, statins enhanced the anti-HCV effect of interferon in combination. Statins may be a promising candidate for the adjuvant in interferon therapy and may improve the efficiency of the current interferon and ribavirin therapy.",
keywords = "Cell culture system, Hepatitis C virus (HCV), Interferon, Life style-related disease, Statin",
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AU - Kato, Nobuyuki

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AB - Hepatitis C virus (HCV) infection causes chronic hepatitis and leads to liver fibrosis and hepatocellular carcinoma. Pegylated-interferon and ribavirin is the current standard therapy for chronic hepatitis C. However, the therapy is only effective in 50% of the patients. To overcome this problem, we recently developed the HCV cell culture system (OR6 system) for the screening of anti-HCV reagents. In this OR6 system, the luciferase gene was introduced into the upstream portion of the HCV genome to facilitate the monitoring of HCV RNA replication. Recently lipid metabolism is reported to be involved in HCV RNA replication. Cholesterol and sphingolipid are the major components in lipid rafts, which seem to be the scaffold for HCV RNA replication. Statins inhibit cholesterol biosynthesis and also have the pleiotropic effects by the inhibition of prenylation. We demonstrated different anti-HCV effects of statins (atorvastatin, simvastatin, fluvastatin, lovastatin, and pitavastatin) using the OR6 system. Surprisingly, in contrast to the other statins, pravastatin exhibited no anti-HCV effect. Furthermore, statins enhanced the anti-HCV effect of interferon in combination. Statins may be a promising candidate for the adjuvant in interferon therapy and may improve the efficiency of the current interferon and ribavirin therapy.

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