HIV-1 Gag polyprotein CA-SP1 cleavage site (CA-SP1 junction)

The HIV-1 Gag polyprotein CA-SP1 cleavage site is a critical junction within the Gag precursor protein, located between the capsid (CA) and spacer peptide 1 (SP1) domains (Source: nih.gov, mdpi.com). During the late stages of the HIV-1 life cycle, the viral protease cleaves the Gag polyprotein at multiple sites to transform an immature, non-infectious budded particle into a mature, infectious virion (Source: nih.gov, researchgate.net). The CA-SP1 cleavage is the final and rate-limiting step in this maturation process, essential for the formation of the conical viral core (Source: nih.gov, pnas.org). Drugs known as maturation inhibitors (MIs) specifically target this site by binding to the CA-SP1 junction, which sterically blocks the HIV-1 protease from accessing the cleavage site (Source: nih.gov, wikipedia.org). This inhibition results in the release of defective, immature virus particles that are unable to infect new host cells (Source: nih.gov, researchgate.net). Consequently, this site represents a validated therapeutic target for antiretroviral therapy, particularly for patients with multi-drug resistant HIV-1 (Source: nih.gov, mdpi.com).

Other names

CA-p2 cleavage siteCapsid-Spacer Peptide 1 junctionGag CA-SP1 junctionp25-p24 cleavage siteCA-SP1 processing site

Maturation inhibitors bind to the CA-SP1 junction of the Gag polyprotein, sterically hindering the HIV-1 protease from cleaving this specific site. This prevents the final step of viral maturation, leading to the production of immature, non-infectious virus particles.