FIG. 7.

Model for Nef-induced MHC-I downmodulation. HIV-1 Nef binds to the cytoplasmic domain of MHC-I, resulting in both accelerated internalization from the plasma membrane (38) and a block of transport to the cell surface. Subsequently, MHC-I is degraded in an acidic compartment (38) or recycled from endosomes to the TGN (14, 22, 33, 44). Nef may accomplish this by acting as an adaptor protein that links MHC-I to other molecules involved in protein transport such as PACS-1 (33), adaptor protein complexes (AP-1, -2, or -3) (22), vacuolar ATPase (25), or PI 3-kinase (44). However, the existence of a complex between MHC-I, Nef, and another Nef-binding protein has not yet been demonstrated.