Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes.
Persistent infection of hepatitis C virus (HCV) is a major cause of liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Searching for a substance with anti-HCV potential, we examined the effects of a variety of compounds on HCV replication using a HCV subgenomic replicon cell culture system. Consequently, the immunosuppressant cyclosporin A (CsA) was found to have a suppressive effect on the HCV replicon RNA level and HCV protein expression in these cells. CsA also inhibited multiplication of the HCV genome in a cultured human hepatocyte cell line infected with HCV using HCV-positive plasma. This anti-HCV activity of CsA appeared to be independent of its immunosuppressive function. In conclusion, our results suggest that CsA may represent a new approach for the development of anti-HCV therapy.
Watashi
Koichi
K
Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto, Japan.
Hijikata
Makoto
M
Hosaka
Masahiro
M
Yamaji
Masashi
M
Shimotohno
Kunitada
K
D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D016679:Genome, Viral; D016174:Hepacivirus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D012313:RNA / Q000037:antagonists & inhibitors; D012093:Replicon / Q000235:genetics; D015398:Signal Transduction; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D014764:Viral Proteins; D012313:RNA; D007371:Interferon-gamma; D016572:Cyclosporine