HIV-1 group-specific antigen polyprotein (Gag)

The HIV-1 group-specific antigen polyprotein (Gag) is the primary structural precursor protein of HIV-1, essential for the assembly, budding, and release of virus particles. Synthesized as a 55-kDa polyprotein (Pr55Gag), it contains multiple functional domains: MA (matrix) mediates membrane binding and targeting, CA (capsid) forms the viral core shell, NC (nucleocapsid) binds and packages viral RNA, p6 is crucial for particle budding via ESCRT recruitment, and two small spacer peptides (SP1, SP2) facilitate domain interactions and particle assembly. During or after budding, Gag is cleaved by the viral protease at defined sites, driving morphological maturation of the particle and generating infectious virions. Targeting Gag, especially the cleavage process—such as at the CA-SP1 junction—is a validated strategy for antiviral drug development, with several maturation inhibitors under investigation or in clinical use[1][2][3][4][5][6][7].

Other names

HIV-1 GagPr55GagGroup-specific antigenGag precursorHIV-1 Gag polyprotein

Drugs such as maturation inhibitors bind to and stabilize specific domains (e.g., CA-SP1 junction), blocking proteolytic cleavage and preventing maturation of the virion into an infectious form[2][5][7]. Protease inhibitors block the viral protease, thereby preventing cleavage of Gag into its functional domains (indirectly targets Gag)[1][5].