HIV-1 reverse transcriptase translocation step (HIV-1 RT)

HIV-1 reverse transcriptase is a multifunctional enzyme critical for replication of HIV-1. It converts the single-stranded viral RNA genome into a double-stranded DNA copy, which is then integrated into the host genome. RT is a heterodimer with p66 (polymerase and RNase H active sites) and p51 (structural) subunits. During DNA synthesis, RT translocates along the nucleic acid substrate, moving the primer terminus for each new nucleotide addition. This translocation is an essential mechanistic step for viral replication[1][2][3][5][7]. RT is a major target for antiretroviral therapy, with two principal drug classes (NRTIs and NNRTIs) and additional inhibitors under development. Drug-resistant variants and translocation-defective inhibitors are the focus of ongoing research. The "translocation step" describes a phase in RT’s activity and is not a molecule itself[2][3][5][7].

Other names

Human immunodeficiency virus type 1 reverse transcriptaseHIV reverse transcriptaseRTHIV-1 RT

NRTIs: Mimic natural nucleotides, are incorporated by RT into the nascent DNA chain, and prevent further chain extension due to missing 3′-OH (chain termination). NNRTIs: Bind to an allosteric site on RT, inducing conformational changes that inhibit polymerase activity and prevent proper translocation. Translocation-defective inhibitors: Prevent the movement (translocation) of RT required for nucleotide incorporation, blocking DNA synthesis.