Human immunodeficiency virus type 1 and Hepatitis B virus reverse transcriptase (HIV-1/HBV RT)

HIV-1 and HBV reverse transcriptases are essential viral enzymes responsible for converting viral RNA (in HIV-1) or pregenomic RNA (in HBV) into double-stranded DNA, a critical step for viral integration and replication within the host cell (UniProt, 2023). While HIV-1 RT is a heterodimer composed of p66 and p51 subunits, the HBV RT is a domain within the larger HBV polymerase (P protein) that also possesses protein-priming and RNase H activities (PubMed, 2020). These enzymes are primary targets for antiviral therapy, particularly because several nucleoside and nucleotide analogues exhibit dual inhibitory activity against both viruses, which is vital for managing patients with HIV/HBV co-infection (NIH, 2022). Inhibition of these enzymes effectively halts the production of new viral particles, reducing viral load and slowing disease progression to AIDS or chronic liver failure. However, the high mutation rate of these viruses often leads to the emergence of drug-resistant variants, necessitating combination therapy and continuous monitoring of viral biomarkers (Nature Reviews Microbiology, 2021).

Other names

HIV-1 reverse transcriptaseHBV polymeraseHBV reverse transcriptaseRNA-directed DNA polymeraseP protein (HBV)p66/p51 heterodimer (HIV-1)

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) act as chain terminators by competing with natural dNTPs for incorporation into the growing viral DNA strand, lacking a 3'-hydroxyl group necessary for further phosphodiester bond formation (StatPearls, 2023). Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) bind to an allosteric site on the HIV-1 RT enzyme, inducing a conformational change that inhibits catalytic activity (PubMed, 2021).