Mutations in HIV-1 gag and pol compensate for the loss of viral fitness caused by a highly mutated protease.

ABSTRACT: During the last few decades, the treatment of HIV-infected patients by highly active antiretroviral therapy, including protease inhibitors (PIs), has become standard. Here, we present results of analysis of a patient-derived, multiresistant HIV-1 CRF02_AG recombinant strain with a highly mutated protease (PR) coding sequence, where up to 19 coding mutations have accumulated in the PR. The results of biochemical analysis in vitro showed that the patient-derived PR is highly resistant to most of the currently used PIs and that it also exhibits very poor catalytic activity. Determination of the crystal structure revealed prominent changes in the flap elbow region and S1/S1' active site subsites. While viral loads in the patient were found to be high, the insertion of the patient-derived PR in

SUBMITTER: Kozisek M 

PROVIDER: S-EPMC3421615 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature