HIV-1 Gag-Pol polyprotein (Gag-Pol) (Gag-Pol)

The HIV-1 Gag-Pol polyprotein is a 160 kDa precursor protein essential for the replication and maturation of the Human Immunodeficiency Virus type 1 (UniProt: P03367). It is generated through a -1 ribosomal frameshifting event during translation of the gag gene, occurring at a frequency of approximately 5% relative to the Gag protein (PubMed: 22534801). This polyprotein contains the structural proteins of the viral core as well as the essential viral enzymes: protease (PR), reverse transcriptase (RT), and integrase (IN). During the process of viral budding and maturation, the PR domain cleaves the polyprotein into its individual functional components, a step that is mandatory for the virus to become infectious (NIH: ClinicalInfo). Because it encodes the entire enzymatic machinery of the virus, Gag-Pol is the primary target for the majority of antiretroviral drugs. Protease inhibitors, reverse transcriptase inhibitors, and integrase inhibitors all function by binding to specific domains within this polyprotein or its cleavage products to disrupt the viral life cycle (PubMed: 30103351). Consequently, it remains the most significant therapeutic target in the management of HIV/AIDS.

Other names

Pr160Gag-PolGag-Pol fusion proteinHIV-1 Gag-Pol polyproteinP03367

Antiretroviral drugs target specific enzymatic domains within the Gag-Pol polyprotein or its processed forms: Protease Inhibitors (PIs) bind to the PR domain to prevent polyprotein cleavage; Nucleoside and Non-Nucleoside Reverse Transcriptase Inhibitors (NRTIs/NNRTIs) inhibit the RT domain to halt viral DNA synthesis; and Integrase Strand Transfer Inhibitors (INSTIs) block the IN domain to prevent the integration of viral DNA into the host genome (NIH: ClinicalInfo; PubMed: 30103351).