Sa. Swann et al., HIV-1 nef blocks transport of MHC class I molecules to the cell surface via a Pl 3-kinase-dependent pathway, VIROLOGY, 282(2), 2001, pp. 267-277
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 t
he level of cell surface major histocompatibility complex class I (MHC-I) p
rotein expression. thus protecting HIV-infected cells from anti-HIV cytotox
ic T lymphocyte (CTL) recognition and killing. Nef also reduces cell surfac
e levels of the HIV receptor, CD4, by accelerating endocytosis. We show her
e 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 dive
rts MHC-I proteins into a PI 3-kinase-dependent transport pathway that prev
ents expression on the cell surface, (C) 2001 Academic Press.