HIV-1 Gag polyprotein capsid-spacer peptide 1 junction (CA-SP1 junction)

The HIV-1 Gag polyprotein CA-SP1 junction is a critical structural and regulatory site involved in the final stage of the HIV-1 life cycle known as maturation. During this phase, the Gag polyprotein precursor is proteolytically processed by the viral protease into its constituent proteins: matrix, capsid, nucleocapsid, and p6. The cleavage at the junction between the capsid (CA) and spacer peptide 1 (SP1) is the final, rate-limiting step that triggers the structural rearrangement of the viral core into its mature, infectious conical shape (Ganser-Pornillos & Pornillos, 2019).\n\nMaturation inhibitors (MIs) are a class of antiretroviral agents that specifically target this junction by binding to the Gag hexameric lattice, thereby sterically hindering the protease from accessing the CA-SP1 cleavage site (Salzwedel et al., 2007). This results in the production of defective, immature viral particles that are incapable of infecting new host cells. Although MIs represent a potent therapeutic strategy, their efficacy is often challenged by naturally occurring polymorphisms in the SP1 region, such as the V7A mutation, which can confer high-level resistance (Spinosa et al., 2020).

Other names

CA-SP1 cleavage siteGag CA-SP1 junctionHIV-1 maturation inhibitor target sitep24-p2 junction

Maturation inhibitors bind to the CA-SP1 junction of the Gag polyprotein, which stabilizes the Gag hexameric lattice and sterically prevents the HIV-1 protease from performing the final cleavage step required for viral infectivity (Ganser-Pornillos & Pornillos, 2019; Salzwedel et al., 2007).