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 language | English |
|---|---|
| Pages (from-to) | 145-150 |
| Number of pages | 6 |
| Journal | Journal of Pharmacological Sciences |
| Volume | 105 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2007 |
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Keywords
- Cell culture system
- Hepatitis C virus (HCV)
- Interferon
- Life style-related disease
- Statin
ASJC Scopus subject areas
- Pharmacology
Cite this
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. / Ikeda, Masanori; Kato, Nobuyuki.
In: Journal of Pharmacological Sciences, Vol. 105, No. 2, 2007, p. 145-150.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Life style-related diseases of the digestive system
T2 - Cell culture system for the screening of anti-hepatitis C virus (HCV) reagents: Suppression of HCV replication by statins and synergistic action with interferon
AU - Ikeda, Masanori
AU - Kato, Nobuyuki
PY - 2007
Y1 - 2007
N2 - 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.
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.
KW - Cell culture system
KW - Hepatitis C virus (HCV)
KW - Interferon
KW - Life style-related disease
KW - Statin
UR - http://www.scopus.com/inward/record.url?scp=36148976383&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36148976383&partnerID=8YFLogxK
U2 - 10.1254/jphs.FM0070050
DO - 10.1254/jphs.FM0070050
M3 - Article
C2 - 17928739
AN - SCOPUS:36148976383
VL - 105
SP - 145
EP - 150
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 2
ER -