Activation pathways and human immunodeficiency virus type 1 replication are not altered in CD4+ T cells expressing the nef protein.
While recent studies in Rhesus monkeys have pointed out the importance of an intact nef gene for the development of acquired immunodeficiency syndrome (AIDS), no biological function has been so far unambiguously attributed to its product. Since Nef has been described to possess GTP-binding properties and to down-regulate CD4 cell surface expression, we looked for evidences of Nef interfering with the transduction of activating signals in human CD4+ T cells. We used a murine leukemia retroviral vector to express the HIV-1BRU nef gene in two permanent tumoral T-cell lines (CEM and Jurkat) and in two nonimmortalized, interleukin-2 (IL2)-dependent, T-cell clones. The single copy recombinant provirus integrated in the genome of these cells directed the synthesis of a 27-kD protein with a half-life greater than 5 h. The levels of expression of cell surface molecules involved in T-cell functions (CD4, CD3, CD28, CD29, IL-2 receptor) were not modified in cell populations expressing Nef. In immunocompetent T-cell clones, cell proliferation and lymphokine production in response to activating stimuli (IL-2, alloantigens, phorbol esters, or antibodies directed against CD2, CD3, CD4, CD28) remained unmodified. Moreover, the presence of Nef did not change the kinetics of human immunodeficiency virus (HIV) infection.
Laboratoire Rétrovirus et Transfert Génétique, Institut Pasteur, Paris, France.
O
O
Schwartz
F
F
Arenzana-Seisdedos
J M
JM
Heard
O
O
Danos
D016475:3T3 Cells; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology*; D002460:Cell Line; D015693:Gene Products, nef / Q000235:genetics / Q000502:physiology*; D015754:Genes, nef; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D014162:Transfection; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
D000954:Antigens, Surface; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus