Human immunodeficiency virus reverse transcriptase (HIV-RT) (HIV-RT)

Human immunodeficiency virus reverse transcriptase (HIV-RT) is a viral enzyme responsible for converting the single-stranded RNA genome of HIV into double-stranded DNA (UniProt: P03366). This process, known as reverse transcription, is a critical step in the viral life cycle, allowing the viral genetic material to integrate into the host cell's genome (NIH: HIV/AIDS Glossary). HIV-RT is a heterodimer composed of p66 and p51 subunits and exhibits three enzymatic activities: RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H (PubMed: 12142021). As a central component of viral replication, it is a major target for antiretroviral therapy (StatPearls: HIV-1 Reverse Transcriptase Inhibitors). Drugs like lamivudine (3TC) are nucleoside analogs that, after intracellular phosphorylation, are incorporated into the nascent DNA strand by HIV-RT, leading to premature chain termination (PubChem: CID 60825). However, the high mutation rate of HIV often leads to the emergence of drug-resistant variants, such as the M184V mutation which confers high-level resistance to lamivudine (Stanford HIV Drug Resistance Database).

Other names

HIV-1 reverse transcriptaseHIV-2 reverse transcriptaseRNA-directed DNA polymerasep66/p51 heterodimerReverse transcriptaseRTRetrotanscriptase

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) like lamivudine act as competitive inhibitors and chain terminators; they are incorporated into the viral DNA chain, lacking a 3'-hydroxyl group, which prevents further elongation (StatPearls: HIV-1 Reverse Transcriptase Inhibitors). Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) bind to a hydrophobic pocket near the active site, causing a conformational change that inhibits polymerization (PubMed: 12142021).