HCV genotype 1b chimeric replicon with NS5B of JFH-1 exhibited resistance to cyclosporine A

Ken ichi Abe, Masanori Ikeda, Yasuo Ariumi, Hiromichi Dansako, Takaji Wakita, Nobuyuki Kato

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Cyclosporine A (CsA) is a well-characterized anti-HCV reagent. Recently it was reported that the genotype 2a JFH-1 strain was more resistant than genotype 1 HCV strains to CsA in a cell culture system. However, the JFH-1 responsible region for the resistance to CsA remains unclear. It was also demonstrated that in genotype 1b HCVs, NS5B interacts with cyclophilin (CyP). To clarify whether or not NS5B of JFH-1 is significant for CsA resistance, we developed a chimeric replicon with NS5B of JFH-1 in the genotype 1b backbone. The chimeric replicon was more resistant to CsA than the parental genotype 1b replicon. Furthermore, reduction of CyPA had a greater effect on HCV RNA replication and sensitivity to CsA than reduction of CyPB. Here, we demonstrated that NS5B of JFH-1 contributed to this strain's CsA-resistant phenotype. NS5B and CyPA are significant for determining HCV's sensitivity to CsA.

Original languageEnglish
Pages (from-to)1671-1677
Number of pages7
JournalArchives of Virology
Volume154
Issue number10
DOIs
Publication statusPublished - Oct 2009

ASJC Scopus subject areas

  • Virology

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