HIV NEF
interacts with host cell signal transduction proteins, downregulates
expression of cell-surface proteins (CD4 and MHC Class I), and can
induce apoptosis in non-infected cells.
increases rate of CD4 endocytosis and lysosomal degradation (Ref. #8)
induce expression of the Fas ligand (Ref. #15)
prevent
apoptosis by interacting with Apoptosis Signal-Regulating Kinase 1
(ASK1), which is involved in apoptotic signaling by TNF and Fas-ligand
(Ref. #15)
increases efficiency of reverse transcription
enhances serine phosphorylation of HIV Matrix protein
Additional
Information:
also known as F-protein
also known as 3'ORF
Nef is packaged into virions, where it is cleaved by viral protease during virion maturation (Ref. #13)
Nef has been shown to bind to a subset of the Src family of kinases (Ref. #5)
Nef is expressed from multiply-spliced mRNA (therefore is Rev-independent)
Nef is expressed early in HIV life cycle
Nef is the first viral protein to accumulate to detectable levels in cell following cellular infection (Ref. #6)
CD4
downregulation is beneficial for HIV infectivity, since excess CD4 on
the cell surface inhibits Env incorporation and virion budding (Ref. #9
& #10)
Class I MHC downregulation is beneficial, since it decreases the efficiency of death by cytotoxic T cells (Ref. #11)
Nef has an negative effect on the induction of NF-kappa-beta (transcription factor) on IL-2 expression (Ref. #12)
CD4 downregulation and increased viral infectivity are genetically distinct, and relate to different domains (Ref. #14)
Apoptosis
of uninfected cells may be induced through the expression of the Fas
ligand on the surface of HIV-infected cells, stimulating the
Fas-dependent apoptotic pathway in cells that come in contact with the
ligand (Ref. #15)
Interactions between Nef and
ASK1 prevent phosphorylation of downstream MAP kinases and JNK kinases
involved in apoptotic signaling (Ref. #15)
Nef
mimics the action of a CD40 ligand, stimulating B cells to express cell
surface receptors (CD22, CD34, and CD58) that induce resting CD4 cells
to become active
Nef is involved in the control of synctia formation
Length:
123 amino acids Molecular Weight: 13692 Da Theoretical pI: 6.42 Gene Description:
This isolate contains a mutation in position 124, which produces a stop
codon. The HXB2 NEF isolate is much shorter than other isolates (~210
aa). Nef is encoded by a single exon that extends into the 3'LTR.
A negatively charged Glutamic acid in Nef interacts with the cytoplasmic tail of CD4 and a dileucine repeat in its membrane proximal region - (Ref. #8)
The
Nef/CD4 binding site overlaps the second alpha-helix, and links
alpha-helix 1 and alpha-helix 2 of Nef. This region contains a
hydrophobic patch, which is centered at the HIV protease cleavage site (Trp57, Leu58, Glu59)
Nef interacts with Apoptosis Signal-Regulating Kinase (ASK1) (Ref. #15)
