Human immunodeficiency virus type 1 reverse transcriptase enzyme (HIV-1 RT)

Human immunodeficiency virus type 1 reverse transcriptase enzyme (HIV-1 RT) is a multifunctional enzyme vital for HIV-1 replication and pathogenesis. It catalyzes the transcription of the single-stranded viral RNA genome into double-stranded DNA, a process necessary for proviral integration into the host genome. HIV-1 RT functions as an asymmetric heterodimer comprising p66 (containing both the DNA polymerase and RNase H active sites) and p51 (mainly structural). Its activities include RNA-dependent and DNA-dependent DNA polymerization and degradation of viral RNA via intrinsic RNase H. HIV-1 RT is a primary target for antiretroviral therapy, with two major drug classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), which act as chain terminators, and non-nucleoside reverse transcriptase inhibitors (NNRTIs), which bind allosterically to disrupt enzyme function. While numerous RT inhibitors form the backbone of most antiretroviral regimens for HIV/AIDS, rapid emergence of drug resistance and associated toxicities pose ongoing therapeutic challenges.

Other names

HIV-1 reverse transcriptaseHIV-1 RTReverse transcriptase of HIV-1

Chain termination during viral DNA synthesis (NRTIs, by incorporation as faulty substrates, blocking DNA elongation); Allosteric inhibition of polymerase activity (NNRTIs, by binding to a hydrophobic pocket and inducing conformational changes that prevent DNA synthesis); Inhibition of RNase H activity (some experimental/novel inhibitors); Non-competitive inhibition (NNRTIs); Active-site binding (NRTIs).