Protease inhibitor-resistant hepatitis C virus mutants with reduced fitness from impaired production of infectious virus.

ABSTRACT:

Background & aims

Several small molecule inhibitors of the hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease have advanced successfully to clinical trials. However, the selection of drug-resistant mutants is a significant issue with protease inhibitors (PIs). A variety of amino acid substitutions in the protease domain of NS3 can lead to PI resistance. Many of these significantly impair the replication fitness of HCV RNA replicons. However, it is not known whether these mutations also adversely affect infectious virus assembly and release, processes in which NS3 also participates.

Methods

We studied the impact of 25 previously identified PI-resistance mutations on the capacity of genotype 1a H77S RNA to replicate in cell culture and produce infectious virus.

SUBMITTER: Shimakami T 

PROVIDER: S-EPMC3155954 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature