Intracellular Destinies: Degradation, Targeting, Assembly, and Endocytosis of HIV Gag

The HIV-1 Gag protein assembles into immature capsids when expressed in human cells. Althoughself-assembly of Gag was once thought to be sufficient to explain capsid formation, in the past decadeit has become increasingly apparent that in cells, the pathway from Gag synthesis to assembledcapsids is coordinated and facilitated by host factors. These cellular factors likely direct the trafficking,membrane targeting, and multimerization of Gag, and could also assist with encapsidation ofviral RNA. While some of these factors have been identified, much remains to be learned about themechanisms by which they act to promote capsid formation. Moreover, studies suggest that theamount of intracellular Gag undergoing assembly per se at any given time may be quite low, withthe majority of Gag in some cell types undergoing degradation or representing Gag that remainscell-associated after assembly. If this model holds true, then defining the Gag subpopulations onwhich individual cellular factors act will be important for understanding the role of host factors. Towardsthis end, it will be important to find markers and features that can distinguish subpopulationsof Gag destined for different outcomes so that these populations can be quantified and trackedseparately both at the biochemical and microscopic level. Thus, the challenge for the future will beto understand which cellular factors act during the pathway from Gag synthesis to assembly, andexactly where and how they act in this pathway.