Human immunodeficiency virus 1 polymerase polyprotein (Pol)

The Human immunodeficiency virus 1 (HIV-1) polymerase polyprotein, commonly known as Pol or Gag-Pol, is a large precursor protein essential for the replication and infectivity of the virus. It is synthesized through a programmed -1 ribosomal frameshift during the translation of viral mRNA, resulting in a fusion protein that contains the viral enzymes (UniProt: P03366). This polyprotein is subsequently processed by the viral protease into three distinct functional enzymes: protease (PR), reverse transcriptase (RT), and integrase (IN). These enzymes are responsible for converting the viral RNA genome into double-stranded DNA, integrating that DNA into the host cell's genome, and cleaving viral polyproteins to allow for the maturation of new virions (PubMed: 12186102). Because these enzymatic activities are vital for the viral life cycle and lack direct human homologs, they are the primary targets for modern antiretroviral therapy (ART). Current treatment regimens typically combine multiple drugs targeting different components of this polyprotein, such as protease inhibitors, reverse transcriptase inhibitors, and integrase strand transfer inhibitors, to suppress viral replication and prevent the emergence of resistance (StatPearls: NBK541089).

Other names

Gag-Pol polyproteinPol polyproteinP160 polyproteinHIV-1 PolRetrovirus-type RNA-directed DNA polymerase

Inhibition of viral protease to prevent the cleavage of polyprotein precursors into functional proteins; competitive or non-competitive inhibition of reverse transcriptase to block the synthesis of viral DNA from RNA; and inhibition of integrase strand transfer to prevent the insertion of the viral genome into the host cell DNA.