HIV Type 1 Gag as a Target for Antiviral Therapy

Abstract

The Gag proteins of HIV-1 are central players in virus particle assembly, release, and maturation, and also function in the establishment of a productive infection. Despite their importance throughout the replication cycle, there are currently no approved antiretroviral therapies that target the Gag precursor protein or any of the mature Gag proteins. Recent progress in understanding the structural and cell biology of HIV-1 Gag function has revealed a number of potential Gag-related targets for possible therapeutic intervention. In this review, we summarize our current understanding of HIV-1 Gag and suggest some approaches for the development of novel antiretroviral agents that target Gag.

Cryo-electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly

“…Essentially all stages of the viral lifecycle have been proposed as potential targets for antiretroviral drugs (15), including assembly and cleavage of the immature virus. In the absence of structural data on the immature Gag lattice, the binding sites of assembly inhibitors relative to the protein-protein interfaces remain unknown.…”

“…This stretch encompasses the CA-SP1 proteolytic cleavage site, mutation of which abolishes formation of mature cores and infectious viruses (14). The bevirimat class of HIV-1 assembly inhibitors blocks HIV-1 replication by specifically targeting processing at this site (15). The structure of this important region of Gag has not yet been resolved with high resolution, however.…”

Cloning, Expression and Purification of a Novel Multi-epitopic HIV-1 Vaccine Candidate: A Preliminary Study on Immunoreactivity

“…Two weeks after the final immunization, a total number of 4×10 6 splenocytes were seeded in a 24-well plate using a complete RPMI-1640 medium, stimulated in vitro with 10 μg/ml of recombinant protein and incubated at 37°C in 5% CO2. Three days post antigen recall, supernatants were collected and centrifuged at 300 x g for 10 min and stored at -70°C for cytokine analysis.…”

“…Among the HIV-1 antigens Gag, Tat, Pol and Env have received considerable attention due to their critical roles in viral life cycle. The Gag protein is essential for HIV-1 virus particle assembly [6]. The most important role of this protein is in the late stages of HIV replication, assembly, maturation and release of a mature viral particle [7].…”

Rustless translation

“…It is likely that there is a competition between Gag translation and Gag mediated packaging. In fact, Gag regulates its own translation, with low concentrations stimulatory and higher concentrations inhibitory (Waheed and Freed , 2012 ). Thus, it is plausible that the interaction of Gag with ABCE1 helps to regulate and coordinate the molecular conflict between translation and packaging of full length viral RNA.…”