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Human immunodeficiency virus 1 reverse transcriptase and Hepatitis B virus reverse transcriptase (HIV-1 RT (for HIV-1 reverse transcriptase), HBV RT (for hepatitis B virus reverse transcriptase))

Target
HIV-1 RT (for HIV-1 reverse transcriptase), HBV RT (for hepatitis B virus reverse transcriptase)
Molecular classification
Enzyme, Polymerase, Viral reverse transcriptase, RNA-dependent DNA polymerase, Ribonuclease H (RNase H) activity
01

Overview

**Reverse transcriptase** is a viral enzyme found in both HIV-1 (a retrovirus) and hepatitis B virus (a hepadnavirus) that catalyzes the transcription of viral RNA into DNA, a critical step in the viral life cycle[1][3][4][5]. HIV-1 reverse transcriptase is a heterodimeric protein with DNA polymerase and RNase H activities, enabling conversion of viral RNA into double-stranded DNA, which is then integrated into the host genome[1][3][5]. HBV reverse transcriptase, encoded within the HBV polymerase, also possesses reverse transcriptase and RNase H activities, and is responsible for converting pregenomic RNA into partially double-stranded DNA within nucleocapsids[4][5][8]. Both enzymes are essential for viral replication and are major therapeutic targets: multiple classes of antiretroviral drugs (notably NRTIs and NNRTIs) inhibit these enzymes, and resistance often arises due to mutations in the viral RT gene[2][4][6][7]. The two enzymes share a common mechanism but are distinct proteins with unique resistance and drug interaction profiles. The widespread use of reverse transcriptase inhibitors for HIV/AIDS and chronic hepatitis B underlines the clinical importance of these enzymes as therapeutic targets[6][4].

Other names
HIV reverse transcriptaseHBV reverse transcriptaseHIV-1 RTHBV RTHIV-1 polymeraseHepatitis B polymeraseViral reverse transcriptase
02

Mechanism of action

Inhibition of DNA polymerase activity (NRTIs/NNRTIs inhibit the ability of reverse transcriptase to synthesize DNA from RNA); Termination of DNA chain elongation (many NRTIs act as chain terminators when incorporated); Direct allosteric inhibition (NNRTIs bind to non-catalytic sites and inhibit conformational changes necessary for enzymatic function); Competitive inhibition with natural substrates (NRTIs compete with natural nucleotides)

03

Biological functions

Viral genome replicationReverse transcription (conversion of viral RNA to DNA)Enzyme-mediated DNA polymerizationRNase H activity (cleavage of RNA in RNA/DNA hybrids)Integration of viral genetic material into host genome (HIV-1)
04

Disease associations

Infection (HIV/AIDS)Infection (Chronic hepatitis B)Antiviral drug resistance
05

Safety considerations

Development of antiviral drug resistance (notably M184V/I, M204V/I, others)Mitochondrial toxicity (class effect of some NRTIs)Liver toxicity and lactic acidosis (NRTIs)Hypersensitivity reactions (e.g., abacavir - HIV RT therapy)Renal toxicity (tenofovir)Risk of HBV flare upon discontinuation of therapy in HBV/HIV co-infected individuals
06

Interacting drugs

Lamivudine (3TC)

12 more in the full profile.

07

Biomarkers

HIV-1 RNA viral load (for monitoring efficacy in HIV)HBV DNA levels (for monitoring efficacy in HBV)Resistance mutations (e.g., M184V in HIV-1 RT, M204V/I in HBV RT)Serologic markers (e.g., HBsAg for HBV)

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