title: Evidence for the role of human immunodeficiency virus type 1 Nef protein as a growth inhibitor to CD4+ T lymphocytes and for the blocking of the Nef function by anti-Nef antibodies.
abstract: Human immunodeficiency virus type 1 (HIV-1) can lead to a profound CD4+ T-cell deficiency. To examine the functional role of HIV-1 Nef protein on the marked loss of CD4+ cells, Nef protein was expressed in and purified from Escherichia coli as a fusion protein with T7 phage gene10 product (Nef-gene10). When peripheral blood mononuclear cells (PBMC) from healthy donors were cultivated in the presence of Nef-gene10 or the gene10 product as well as interleukin-2 (IL-2), it was found that the Nef-gene10, but not the gene10 product, induced a remarkable decline in the CD4/CD8 ratio and in the response to phytohaemagglutinin of PBMC as well as of nylon wool-passed purified T cells. Nef-gene10 inhibited the proliferation of CD4+ cells, but did not kill the cells. This suppression of the IL-2-dependent proliferation of CD4+ cells by Nef-gene10 seemed to be due to enhanced production of several lymphokines, especially of interferon-gamma. Thus, Nef protein might be partly responsible for the selective depletion of CD4+ cells in HIV-1 infection. Furthermore, the Nef-induced decline in the CD4/CD8 ratio was interrupted by anti-Nef antibodies, suggesting the possibility that a vaccine which resulted in the production of such functional Nef antibodies would be useful in the treatment of HIV-1-induced immunodysfunction.
authors.affiliation: Institute for Laboratory Animal Research, Nagoya University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017123:Bacteriophage T7 / Q000235:genetics; D001483:Base Sequence; D016516:CD4-CD8 Ratio / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D015693:Gene Products, nef / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015754:Genes, nef / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D008285:Major Histocompatibility Complex / Q000502:physiology; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D010641:Phenotype; D011817:Rabbits; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D000906:Antibodies; D015693:Gene Products, nef; D007376:Interleukin-2; D008024:Ligands; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D014760:Viral Fusion Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus