Diverse effects of cyclosporine on hepatitis C virus strain replication.
Recently, a production system for infectious particles of hepatitis C virus (HCV) utilizing the genotype 2a JFH1 strain has been developed. This strain has a high capacity for replication in the cells. Cyclosporine (CsA) has a suppressive effect on HCV replication. In this report, we characterize the anti-HCV effect of CsA. We observe that the presence of viral structural proteins does not influence the anti-HCV activity of CsA. Among HCV strains, the replication of genotype 1b replicons was strongly suppressed by treatment with CsA. In contrast, JFH1 replication was less sensitive to CsA and its analog, NIM811. Replication of JFH1 did not require the cellular replication cofactor, cyclophilin B (CyPB). CyPB stimulated the RNA binding activity of NS5B in the genotype 1b replicon but not the genotype 2a JFH1 strain. These findings provide an insight into the mechanisms of diversity governing virus-cell interactions and in the sensitivity of these strains to antiviral agents.
Ishii
Naoto
N
Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Watashi
Koichi
K
Hishiki
Takayuki
T
Goto
Kaku
K
Inoue
Daisuke
D
Hijikata
Makoto
M
Wakita
Takaji
T
Kato
Nobuyuki
N
Shimotohno
Kunitada
K
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D016572:Cyclosporine / Q000494:pharmacology*; D016679:Genome, Viral / Q000235:genetics; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000378:metabolism; D012093:Replicon / Q000235:genetics; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D012367:RNA, Viral; D014764:Viral Proteins; D016572:Cyclosporine