Specific suppression of human CD4 surface expression by Nef from the pathogenic simian immunodeficiency virus SIVmac239open.
HIV-1 Nef down-modulates expression of human CD4, the human immunodeficiency virus (HIV) receptor, at the cell surface. Down-modulation of retrovirus receptors has been shown to be important in the survival of infected cells. To relate this observation to AIDS pathogenesis, we compared the ability of Nef from the SIVmac239open and HIV-1 SF2 isolates to suppress CD4 surface levels. We first obtained the simian immunodeficiency virus (SIV)nef gene by PCR and cloned it into the retroviral vector pLXSN. We then established high titer (1 x 10(6) CFU/ml) amphotropic retrovirus producer lines (PA317/LSnefSN). Using LSnefSN we obtained populations of CD4+ human and mouse T-cells, human B-cells, and mouse fibroblasts that expressed SIV or HIV Nef. In the two human cell lines, both HIV and SIV Nef expression correlated with a significant decrease in CD4 cell surface levels. However, Nef expression did not alter the cell surface levels of CD3, CD18, and MHC class I. Both Nef proteins also suppressed human CD4 surface expression in mouse fibroblasts. Interestingly, SIV Nef failed to suppress cell surface expression of mouse CD4 under conditions where HIV-1 Nef did. Human CD4 down-modulation is a conserved function of SIV and HIV Nef likely to be important for pathogenesis.
Foster
J L
JL
Department of Biochemistry, University of Tennessee Health Sciences Center, Memphis 38163.
Anderson
S J
SJ
Frazier
A L
AL
Garcia
J V
JV
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology; D001483:Base Sequence; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D004279:DNA, Viral; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000235:genetics / Q000502:physiology*; D015754:Genes, nef; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D014779:Virus Replication / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D004279:DNA, Viral; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus