Human immunodeficiency virus type 1 clade B Gag polyprotein (Gag)

The HIV-1 clade B Gag polyprotein (Pr55Gag) is the essential structural precursor for the assembly, budding, and maturation of human immunodeficiency virus type 1 (HIV-1) (UniProt: P03367). It coordinates the packaging of the viral genomic RNA and the recruitment of viral and host factors to the site of assembly at the plasma membrane (PubMed: 22334592). Following budding, the viral protease cleaves the Gag polyprotein into mature structural proteins: matrix (MA), capsid (CA), nucleocapsid (NC), and p6, along with two spacer peptides, SP1 and SP2 (NIH: HIV Structural Proteins). This proteolytic processing is critical for the formation of the infectious conical core. Clade B is the dominant HIV-1 subtype in the Americas, Europe, and Australia, making its Gag protein a primary target for drug development (PubMed: 28438834). Therapeutic agents known as maturation inhibitors, such as Bevirimat, target the Gag polyprotein by binding to the CA-SP1 cleavage site, thereby preventing the final step of viral maturation and rendering the virus non-infectious (DrugBank: DB05016).

Other names

Pr55GagGroup-specific antigenGag polyproteinHIV-1 Gag

Maturation inhibitors bind to the Gag polyprotein, specifically at the junction between the capsid (CA) and spacer peptide 1 (SP1), sterically hindering the HIV-1 protease from cleaving this site. This prevents the final step of viral maturation, leading to the release of defective, non-infectious viral particles (PubMed: 28438834).