Reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1 RT)

The reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1 RT) is a multifunctional viral enzyme that mediates the conversion of the single-stranded viral RNA genome into double-stranded DNA, a crucial step for viral integration into the host genome[1][3][4]. It is a heterodimeric enzyme composed of two subunits, p66 and p51, derived from the Gag-Pol polyprotein via proteolytic cleavage. The larger p66 subunit harbors two distinct enzymatic domains: an RNA/DNA-dependent DNA polymerase and an RNase H, while the p51 subunit provides structural support[1][2][3][4]. HIV-1 RT initiates DNA synthesis at the 3′-end of a host-derived tRNA primer annealed to the viral genome and catalyzes the processive synthesis of viral DNA while simultaneously degrading the RNA strand of an RNA/DNA hybrid via its RNase H activity. HIV-1 RT is the molecular target of several classes of antiretroviral drugs, and structural insights have been fundamental in rational drug development. Its high mutation rate is a major contributor to drug resistance, representing a continual challenge for effective long-term antiretroviral therapy[5][6][4].

Other names

Human immunodeficiency virus type 1 reverse transcriptaseHIV reverse transcriptaseRT (in context of HIV-1)HIV-1 RT

Chain termination of nascent viral DNA (NRTIs act as nucleotide analogs, halt elongation after incorporation); Allosteric inhibition of polymerase activity (NNRTIs bind a hydrophobic pocket, disrupt enzyme conformation and function); Direct inhibition of RNase H activity (select experimental antivirals)