Cyclosporine inhibits a direct interaction between cyclophilins and hepatitis C NS5A.

ABSTRACT:

Background

Hepatitis C Virus (HCV) infection is a leading indication for liver transplantation. HCV infection reoccurs almost universally post transplant, decreasing both graft longevity and patient survival. The immunosuppressant, cyclosporine A (CsA) has potent anti-HCV activity towards both HCV replicons and the genotype 2a cell culture infectious virus. Previously, we isolated mutations in the 1bN replicon with less sensitivity to CsA that mapped to both NS5A and NS5B regions of the virus. Mutations in NS5A alone conferred decreased CsA susceptibility regardless of NS5B mutations.

Methodology/principal findings

We examined the mechanisms by which NS5A mutations contribute to CsA resistance and if they are strain dependent. Using in vitro mutagenesis, the amino acid posit

SUBMITTER: Fernandes F 

PROVIDER: S-EPMC2843741 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature