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

HCV genotype 1b chimeric replicon with NS5B of JFH-1 exhibited resistance to cyclosporine A 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

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

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Publisher
Springer Vienna
Copyright
Copyright © 2009 by Springer-Verlag
Subject
Biomedicine; Infectious Diseases; Medical Microbiology ; Virology
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-009-0502-x
Publisher site
See Article on Publisher Site

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.

Journal

Archives of VirologySpringer Journals

Published: Oct 1, 2009

References

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