Human immunodeficiency virus type 1 Gag-Pol polyprotein (Gag-Pol) (Gag-Pol)

The Human immunodeficiency virus type 1 (HIV-1) Gag-Pol polyprotein is a 160 kDa precursor protein essential for the assembly, maturation, and infectivity of the virus (UniProt P03367). It is synthesized via a programmed -1 ribosomal frameshift during translation, resulting in a fusion of the structural Gag proteins with the enzymatic Pol proteins (PubMed: 20113501). This polyprotein contains the viral protease, reverse transcriptase, and integrase, which are the primary enzymatic targets for antiretroviral therapy (NIH: HIV Life Cycle). During viral budding, the protease component auto-cleaves from the polyprotein and subsequently processes the remaining Gag and Gag-Pol precursors into functional units, a process known as maturation (StatPearls: Antiretroviral Therapy). Drugs such as protease inhibitors (PIs) prevent this cleavage, while reverse transcriptase inhibitors (RTIs) and integrase strand transfer inhibitors (INSTIs) target the enzymes derived from this precursor (FDA: Approved HIV Medicines). Consequently, the Gag-Pol polyprotein is the fundamental source of the machinery required for HIV to replicate and integrate into the host genome. Effective inhibition of the enzymes encoded within Gag-Pol has transformed HIV infection from a fatal disease into a manageable chronic condition.

Other names

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

Inhibition of viral protease (preventing polyprotein processing), inhibition of reverse transcriptase (preventing DNA synthesis), and inhibition of integrase (preventing genomic integration).