HIV-1 Gag Protein Nanoparticle Systems: Assembly and Viral Inhibition Strategies

Current drug therapies available to individuals infected with the HIV-1 virus work to target reverse transcriptase and the viral protease via a drug cocktail. However, during the process of maturation in HIV-1, viral protease cleaves Gag and initiates conformational changes in CA proteins which foster its assembly into the capsid, a fullerene shaped shell composed of ~1500 copies of CA. This capsid houses the viral genetic information and poses as a viable target for treatment to combat the virus. Current knowledge of the mechanisms and processes of this conformational shift is very limited. To enhance our understanding of the process of maturation we studied the effects of protein crowding by constructing Gag virus-like particles (VLP’s) alone (control), in the presence of C-terminal capsid, cytochrome-c, lipids, and ribonucleic acid so we can study the effects their presence may have on Gag’s ability to self-assemble. Our results indicate that Gag retains its ability to self-assemble into VLP’s despite protein crowding effects and competitive inhibition of its dimerization interface.