Identification of two intracellular mechanisms leading to reduced expression of oncoretrovirus envelope glycoproteins at the cell surface

All retrovirus glycoproteins have a cytoplasmic domain that plays several r oles in virus replication. We have determined whether and how the cytoplasm ic domains of oncoretrovirus glycoproteins modulate their intracellular tra fficking, by using chimeric proteins that combined the alpha -chain of the interleukin-2 receptor with the glycoprotein cytoplasmic domains of five on coretroviruses: human T-cell leukemia virus type 1 (HTLV-1), Rous sarcoma v irus (RSV), bovine leukemia virus (BLV), murine leukemia virus (MuLV), and Mason-Pfizer monkey virus (MPMV). All of these proteins were synthesized an d matured in the same way as a control protein with no retrovirus cytoplasm ic domain. However, the amounts of all chimeric proteins at the cell surfac e were smaller than that of the control protein. The protein appearing at a nd leaving the cell surface and endocytosis were measured in stable transfe ctants expressing the chimera. We identified two groups of proteins which f ollowed distinct intracellular pathways. Group 1 included chimeric proteins that reached the cell surface normally but were rapidly endocytosed afterw ards. This group included the chimeric proteins with HTLV-1, RSV, and BLV c ytoplasmic domains. Group 2 included chimeric proteins that were not detect ed at the cell surface, despite normal intracellular concentrations, and we re accumulated in the Golgi complex. This group included the chimeric prote ins with MuLV and MPMV cytoplasmic domains. Finally, we verified that the M uLV envelope glycoproteins behaved in the same way as the corresponding chi meras. These results indicate that retroviruses have evolved two distinct m echanisms to ensure a similar biological feature: low concentrations of the ir glycoproteins at the cell surface.