Understanding the molecular mechanism of sequence dependent tenofovir removal by HIV-1 reverse transcriptase: differences in primer binding site versus polypurine tract.

ABSTRACT: Tenofovir (TFV) is a nucleotide reverse transcriptase inhibitor (NtRTI) that is often administered as first-line therapy against human immunodeficiency virus type-1 (HIV-1) infection and acts as a chain terminator when incorporated into viral DNA. However, HIV-1 reverse transcriptase (RT) excises TFV in the presence of either ATP or pyrophosphate, which is an important drug resistance mechanism that would interfere with the effective treatment. Previous studies have shown conflicting results on excision efficiencies for TFV-terminated primer-templates derived from either primer binding site (PBS) or polypurine tract (PPT) sequences. To provide mechanistic insight into the variation in TFV removal from both sequences that are vital for the HIV-1 life cycle, we compared the efficiencies of r

SUBMITTER: Iyidogan P 

PROVIDER: S-EPMC3398203 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature