Human immunodeficiency virus type 1 group-specific antigen polyprotein (Gag polyprotein) and polymerase polyprotein (Gag-Pol polyprotein) (Gag (for group-specific antigen polyprotein), Gag-Pol (for polymerase polyprotein))

The Gag polyprotein is a ~55 kDa multidomain protein comprising the matrix (MA), capsid (CA), nucleocapsid (NC), spacer peptides (SP1, SP2), and p6 domains. It orchestrates membrane targeting, oligomerization, RNA packaging, and budding of new virions. During HIV-1 replication, Gag is cleaved by the viral protease at five specific sites to yield its functional domains, an essential step for virion maturation and infectivity. The Gag-Pol polyprotein arises by ribosomal frameshifting during translation of Gag and includes the protease (PR), reverse transcriptase (RT), and integrase (IN) enzymes in addition to Gag domains. Gag and Gag-Pol are crucial for constructing the viral particle and for enzymatic functions that allow the virus to replicate its genome, integrate into the host, and mature into an infectious virion. Both are highly validated antiviral drug targets, with numerous classes of inhibitors designed to block their processing or enzymatic activities. The canonical names for these molecules are “Human immunodeficiency virus type 1 group-specific antigen polyprotein (Gag)” and “Human immunodeficiency virus type 1 polymerase polyprotein (Gag-Pol),” with the abbreviations Gag and Gag-Pol, respectively. They are not properly represented as a single target (“HIV-1 group-specific antigen polyprotein and polymerase polyprotein”), so this entry should be split for structured annotation.

Other names

Gag polyproteingroup-specific antigen (Gag)p55Gag-Pol polyproteinPol polyproteinPr160^Gag-Pol

Protease inhibitors block processing of Gag and Gag-Pol polyproteins, preventing maturation of infectious virions; Maturation inhibitors block specific cleavage events (e.g., CA-SP1); Reverse transcriptase inhibitors block viral DNA synthesis; Integrase inhibitors block integration of viral DNA into the host genome