Serine phosphorylation-independent downregulation of cell-surface CD4 by nef.
A decline in the T-cell population usually marks the onset of progressive immunological disease in individuals infected with the human immunodeficiency virus (HIV). Because CD4+ cells help to coordinate efficient immune responses, some of the defects in the immune function in advanced cases of AIDS may be explained by the disappearance of these cells. Therefore, an understanding of the mechanisms used by HIV to induce the reduction of CD4+ cells is important. Here we use a Moloney murine leukaemia virus-based retroviral vector in order to express the nef gene of HIV-1 in three lymphocytic cell lines expressing CD4. In all cases we find that cell-surface CD4 expression is inversely related to nef expression. However, nef does not alter steady-state levels of CD4 RNA or CD4 protein. Also, nef can downregulate a CD4 triple mutant (Ser----Ala) that is neither phosphorylated nor down-regulated by phorbol esters, indicating that nef is acting by a different mechanism.
Garcia
J V
JV
Program in molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Miller
A D
AD
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D015693:Gene Products, nef / Q000235:genetics* / Q000502:physiology; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics*; D016325:HIV Long Terminal Repeat; D006801:Humans; D008979:Moloney murine leukemia virus / Q000235:genetics; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus
D015703:Antigens, CD; D015704:CD4 Antigens; D015693:Gene Products, nef; D012333:RNA, Messenger; D054311:nef Gene Products, Human Immunodeficiency Virus; D010768:Phosphoserine; D013755:Tetradecanoylphorbol Acetate