HIV-1 nef blocks transport of MHC class I molecules to the cell surface via a Pl 3-kinase-dependent pathway

HIV causes a chronic infection by evading immune eradication. A key element of HIV immune escape is the HIV-I Nef protein. Nef causes a reduction in the level of cell surface major histocompatibility complex class I (MHC-I) protein expression. thus protecting HIV-infected cells from anti-HIV cytotoxic T lymphocyte (CTL) recognition and killing. Nef also reduces cell surface levels of the HIV receptor, CD4, by accelerating endocytosis. We show here that endocytosis is not required for Nef-mediated downmodulation of MHC-I molecules. The main effect of Nef is to block transport of MHC-1 molecules to the cell surface, leading to accumulation in intracellular organelles. Furthermore. the effect of Nef on MHC-1 molecules (but not on CD4) requires phosphoinositide 3-kinase (PI 3-kinase) activity. We propose that Nef diverts MHC-I proteins into a PI 3-kinase-dependent transport pathway that prevents expression on the cell surface, (C) 2001 Academic Press.