Human immunodeficiency virus type 1 capsid protein (HIV-1 CA) (HIV-1 CA)

The Human immunodeficiency virus type 1 (HIV-1) capsid protein (CA) is a multifunctional structural protein that forms the protective shell around the viral RNA genome (UniProt P04591). It is initially synthesized as part of the Gag polyprotein and is later cleaved by viral protease to form the mature, cone-shaped capsid (PubMed: 32612214). The CA–CA inter-subunit FG pocket is a highly conserved hydrophobic site located at the interface of the N-terminal domain of one CA subunit and the C-terminal domain of an adjacent subunit (PubMed: 21106746). This pocket is crucial for viral replication as it serves as the binding site for essential host cell factors, such as cleavage and polyadenylation specificity factor 6 (CPSF6) and nucleoporin 153 (NUP153), which facilitate nuclear import and integration (PubMed: 32612214). Therapeutic agents like Lenacapavir target this specific pocket to disrupt multiple stages of the viral life cycle, including capsid assembly, disassembly, and nuclear transport (FDA: Sunlenca). By stabilizing the capsid structure or blocking host factor interactions, these inhibitors effectively halt viral replication.

Other names

p24Gag-p24HIV-1 CA proteinCapsid protein p24FG binding pocketCA-CA interface

Capsid inhibition by binding to the FG binding pocket, which disrupts multiple stages of the viral life cycle including assembly, maturation, and nuclear transport by interfering with host factor interactions such as CPSF6 and NUP153 (PubMed: 32612214, PubMed: 21106746).