HIV-1 Gag polyprotein (Gag) (Gag)

The HIV-1 Gag polyprotein (Pr55Gag) is the essential structural precursor for the assembly, budding, and maturation of HIV-1 particles (UniProt P03367). It coordinates the assembly of viral components at the host cell plasma membrane and the packaging of the viral RNA genome (PubMed: 25635358). Following budding, the viral protease cleaves Gag into mature proteins—matrix (MA), capsid (CA), nucleocapsid (NC), and p6—a process critical for viral infectivity (PubMed: 22457318). Gag is a key target for maturation inhibitors like Bevirimat, which bind to the CA-SP1 junction to prevent final cleavage, resulting in defective, non-infectious virions (PubMed: 19843797). Furthermore, Gag is a primary focus for T-cell-based vaccines because it contains highly conserved epitopes that are frequently targeted by protective immune responses in elite controllers (PubMed: 18495771). The protein's role in both structural integrity and immune recognition makes it a versatile target for both antiretroviral therapy and immunotherapy. However, the clinical development of Gag-targeting drugs has faced challenges due to naturally occurring polymorphisms in the Gag sequence that confer resistance (PubMed: 17908277). Despite these challenges, Gag remains a high-priority target for next-generation HIV therapies aiming for long-term viral suppression or a functional cure.

Other names

Pr55GagGroup-specific antigenp55Gag polyprotein

Maturation inhibition by binding to the CA-SP1 cleavage site, preventing the final step of Gag processing and resulting in non-infectious viral particles (PubMed: 19843797).