Physiological Mg²⁺ Conditions Significantly Alter the Inhibition of HIV-1 and HIV-2 Reverse Transcriptases by Nucleoside and Non-Nucleoside Inhibitors in Vitro.

ABSTRACT: Reverse transcriptases (RTs) are typically assayed in vitro with 5-10 mM Mg²⁺, whereas the free Mg²⁺ concentration in cells is much lower. Artificially high Mg²⁺ concentrations used in vitro can misrepresent different properties of human immunodeficiency virus (HIV) RT, including fidelity, catalysis, pausing, and RNase H activity. Here, we analyzed nucleoside (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) in primer extension assays at different concentrations of free Mg²⁺. At low concentrations of Mg²⁺, NRTIs and dideoxynucleotides (AZTTP, ddCTP, ddGTP, and 3TCTP) inhibited HIV-1 and HIV-2 RT synthesis less efficiently than they did with large amounts of Mg²⁺, whereas inhibition by the "translocation-defective RT inhibito

SUBMITTER: Achuthan V 

PROVIDER: S-EPMC5453313 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature