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

Target
HIV-1 RT
Molecular classification
Enzyme, DNA polymerase (RNA-dependent and DNA-dependent), Ribonuclease H (RNase H), Retroviral polymerase
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Overview

Reverse transcriptase of human immunodeficiency virus (HIV-1 RT) is a multifunctional enzyme central to HIV replication, converting the single-stranded viral RNA genome into double-stranded DNA for integration into the host genome. It is a heterodimer (p66/p51) with two primary enzymatic activities: polymerase (both RNA- and DNA-dependent) and ribonuclease H, which degrades the RNA strand of RNA/DNA hybrids formed during replication. This enzyme is essential for viral proliferation and a principal target of antiretroviral drugs; over half of approved HIV therapies target its activity, either by inhibiting the DNA polymerization process (NRTIs, NNRTIs) or interfering with RNA cleavage. Its structural and functional features, combined with high mutation rates, make it a significant focus for ongoing drug development and resistance monitoring.

Other names
HIV-1 reverse transcriptaseHIV reverse transcriptaseRT (context: HIV)Human immunodeficiency virus reverse transcriptase
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Mechanism of action

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): Incorporate into viral DNA chain, terminate DNA elongation. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Allosterically inhibit polymerase activity by binding to NNRTI pocket. RNase H inhibitors (experimental): Block RNA degradation during reverse transcription.

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Biological functions

Reverse transcription (conversion of viral RNA to dsDNA)Viral genome replicationRNA hydrolysisDNA synthesis (polymerase activity)
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Disease associations

Infection (key for HIV-1/AIDS pathogeny)Antiviral drug target in HIV infection
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Safety considerations

Rapid emergence of drug-resistant mutantsCross-resistance within NRTI and NNRTI classesDrug toxicity (e.g., mitochondrial toxicity for some NRTIs)Hypersensitivity reactions
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Interacting drugs

Zidovudine (AZT)

11 more in the full profile.

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Biomarkers

Mutations in reverse transcriptase gene as resistance markers (e.g. K103N, M184V)Viral load (for therapeutic efficacy)Genotypic resistance tests for clinical monitoring

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