GENETIC REGULATION OF GP120
The HIV-1 envelope glycoprotein is encoded by the env gene, which produces a precursor protein that is 160kDa. This is proteolytically processed into the soluble (gp120) and membrane-spanning (gp41) subunits.
The gene product is produced in the endoplasmic reticulum (ER) as the gp160-precursor protein. This is then folded into trimers and transported out of the ER and then to the Golgi apparatus, where it undergoes further oligosaccharide modifications.16 During transport through the secretory pathways in human T cells, the gp160 is proteolytically cleaved to create the gp120 and gp41 subunits.17 The envelope products are then assembled with the other viral proteins and prepared for virion budding at the cell surface.After leaving the Golgi apparatus, the HIV envelope moves to intracellular granules that are closely regulated by the secretory pathway. Miranda et al.18 demonstrated that large amounts of mature envelope are found stored in intracellular compartments of the cell. As part of the secretory pathway, the HIV gp120 traffics to the intracellular compartment granules that also contain CTLA-4. CTLA-4 is an important negative regulator of T cell immune responses, and its surface expression is tightly controlled as it traffics through the secretory pathways after T cell activation.19 Moreover, the precursor gp160 is proteolytically cleaved into gp120 and gp41 by the PC6 protease, a component of the secretory pathway.
Because HIV gp120 and CTLA-4 share granules in the cell’s secretory pathway on their way to the cell surface, they are expressed together. T cell activation induces cell surface expression of CTLA-4 and gp120.18’20 It is unclear what advantage this colocalization provides HIV or the host T cell. However, it is intriguing to postulate that co-regulation of the gp120 and CTLA-4 could alert the immune system to the presence of the incipient virion and, in turn, may influence T cell activation.