Human immunodeficiency virus type 1 polymerase polyprotein (HIV-1 Pol) (HIV-1 Pol)

The Human immunodeficiency virus type 1 polymerase polyprotein (HIV-1 Pol) is a large precursor protein essential for the replication and maturation of the virus (UniProt P03366). It is cleaved by the viral protease into three distinct enzymes: protease (PR), reverse transcriptase (RT), and integrase (IN) (NIH/NCBI). Protease processes viral polyproteins into functional units; reverse transcriptase converts the viral RNA genome into double-stranded DNA; and integrase facilitates the insertion of this viral DNA into the host cell genome (StatPearls). These three enzymes are the primary targets for the majority of modern antiretroviral therapies, including protease inhibitors, reverse transcriptase inhibitors, and integrase strand transfer inhibitors (PubMed: PMC4924471). While these drugs are highly effective at suppressing viral replication, the high mutation rate of HIV-1 frequently leads to the development of drug resistance, requiring the use of combination therapy (HAART). Understanding the structure and function of the Pol proteins remains critical for the development of next-generation HIV treatments.

Other names

Pol polyproteinHIV-1 polymeraseGag-Pol polyproteinP160

Inhibition of viral protease to prevent polyprotein cleavage and viral maturation; inhibition of reverse transcriptase to block viral RNA-to-DNA synthesis; and inhibition of integrase to prevent the insertion of viral DNA into the host cell genome (StatPearls; NIH).