Target intelligence / Profile preview

Gag polyprotein (HIV-1) (Gag)

Target
Gag
Molecular classification
Viral structural protein, Polyprotein
01

Overview

The Gag polyprotein (Pr55Gag) is the primary structural protein of the Human Immunodeficiency Virus (HIV-1), orchestrating the assembly, budding, and maturation of new virions (UniProt P03367; PMID: 22894348). During the late stages of the viral life cycle, Gag is synthesized in the host cell cytoplasm and recruited to the plasma membrane where it assembles into immature viral particles (PMID: 31548325). Upon budding, the viral protease cleaves Pr55Gag into separate functional subunits: matrix (MA/p17), capsid (CA/p24), nucleocapsid (NC/p7), and p6, alongside spacer peptides SP1 and SP2. This cleavage process, known as maturation, is essential for the virus to become infectious. Therapeutic strategies targeting Gag include maturation inhibitors, which specifically bind to the CA-SP1 cleavage site to prevent final processing, resulting in the production of defective, non-infectious viral particles (PMID: 26424771). Furthermore, Gag is a critical component in therapeutic and prophylactic HIV vaccines because it is highly conserved across different viral clades and contains numerous epitopes that trigger robust CD8+ T-cell responses (PMID: 25160093).

Other names
Pr55GagGroup-specific antigenHIV-1 Gagp55 Gag polyprotein
02

Mechanism of action

Maturation inhibition (blocking the cleavage of CA-SP1 by HIV-1 protease), inhibition of viral assembly, or induction of T-cell mediated immune responses via vaccine-delivered antigens.

03

Biological functions

Viral assemblyViral buddingViral maturationGenomic RNA bindingNuclear-cytoplasmic transport
04

Disease associations

InfectionHuman Immunodeficiency Virus (HIV) infectionAcquired Immunodeficiency Syndrome (AIDS)
05

Safety considerations

High frequency of naturally occurring resistance mutations (polymorphisms) in the Gag cleavage sitesRapid emergence of drug resistance under selective pressureGastrointestinal side effects associated with maturation inhibitors
06

Interacting drugs

Bevirimat

5 more in the full profile.

07

Biomarkers

HIV-1 p24 antigenAnti-Gag antibodiesHIV-1 RNA viral load

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