Gag polyprotein (Gag) (Gag)

The Gag polyprotein is the primary structural component of retroviruses, such as the Human Immunodeficiency Virus (HIV), and is essential for the assembly, budding, and maturation of infectious progeny (UniProt P03367). Synthesized as a precursor protein (Pr55Gag), it migrates to the host cell plasma membrane where it multimerizes to drive the formation of immature viral particles (PubMed: 22534358). During or after budding, the viral protease cleaves Gag into distinct functional proteins: matrix (MA), capsid (CA), nucleocapsid (NC), and p6, along with two spacer peptides, SP1 and SP2 (NIH: PMC3415700). This proteolytic processing, particularly the final cleavage between CA and SP1, is a critical step in viral maturation that transforms the immature particle into an infectious virion. Therapeutic interventions targeting Gag include maturation inhibitors, which bind to the CA-SP1 junction to prevent cleavage, and capsid inhibitors that interfere with the stability and transport of the CA core (PubMed: 32810114). These mechanisms offer a potent means of inhibiting viral replication and are particularly valuable for treating patients with multi-drug resistant HIV strains.

Other names

Group-specific antigenPr55Gagp55Gag-Pol polyprotein precursor

Maturation inhibition by blocking the proteolytic cleavage of the CA-SP1 junction and modulation of capsid assembly/disassembly.