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 typ e 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 pr operty of primary HIV-1 nef alleles. Mutations in conserved amino acid motifs of Nef disrupted CD4 down-regulation. Our observations strongl y suggest that CD4 down-regulation reflects a conserved function of ne f, which is selected in vivo in human HIV-1 infection. Methodology des cribed here provides quantitative assays to establish whether alterati ons in nef correlate with the dynamics of disease progression in human AIDS.