CD4 down-regulation by nef alleles isolated from human immunodeficiency virus type 1-infected individuals.
PCR was used to clone isolates of the human immunodeficiency virus type 1 (HIV-1) nef gene directly from peripheral blood leukocytes of HIV-1-infected individuals. A transient expression system with human CEM T cells was used to assess the effect of nef on CD4 antigen expression on the cell surface. We show that CD4 down-regulation is a frequent property of primary HIV-1 nef alleles. Mutations in conserved amino acid motifs of Nef disrupted CD4 down-regulation. Our observations strongly suggest that CD4 down-regulation reflects a conserved function of nef, which is selected in vivo in human HIV-1 infection. Methodology described here provides quantitative assays to establish whether alterations in nef correlate with the dynamics of disease progression in human AIDS.
Cold Spring Harbor Laboratory, NY 11724.
R
R
Mariani
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J
Skowronski
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism*; D004279:DNA, Viral / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D015536:Down-Regulation; D015693:Gene Products, nef / Q000096:biosynthesis / Q000235:genetics; D015754:Genes, nef; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D004279:DNA, Viral; D015693:Gene Products, nef; D009838:Oligodeoxyribonucleotides; D054311:nef Gene Products, Human Immunodeficiency Virus