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. 2016 Mar 3;8(3):67. doi: 10.3390/v8030067

Figure 3.

Figure 3

CD4 and major histocompatibility complex (MHC)-I are downregulated by HIV-1 Nef protein. Nef downregulates CD4 by recruiting the AP-2 adaptor to link CD4 to clathrin-mediated endocytosis, then targets CD4 for lysosomal degradation via β-COP-containing vesicles. Two mechanisms of Nef-mediated MHC-I downregulation have been proposed. Nef may bind de novo synthesized MHC-I in the TGN as a part of a Nef/AP-1/MHC-I trimolecular complex, eventually resulting in MHC-I lysosomal degradation, possibly along the same final vesicular pathway used for Nef-mediated CD4 degradation. A second model proposes that Nef induces the active removal of MHC-I from the plasma membrane (PM) by inducing a Srk family kinase (SFK)/phosphoinositide-3-kinase (PI-3K) signaling axis, and then prevents the homeostatic recycling of MHC-I molecules back to the cell surface. Instead, Nef induces retrograde transport of MHC-I to the TGN for sequestration. These mechanisms are not mutually exclusive and may occur in concert or at different time periods depending on the cell type.