In vitro cytocidal effects of human immunodeficiency virus type 1 Nef on unprimed human CD4+ T cells without MHC restriction.
We have previously shown that the C-terminal region of human immunodeficiency virus type 1 (HIV-1) Nef antigen present on the outer surface of virus-infected cells has an affinity for uninfected T cells and that the Nef protein is responsible for T cell death. To exclude completely the possibility of MHC restriction of this cytotoxic activity, the in vitro cytotoxic potential of HIV-1 Nef against various CD4+ T cell lines as well as naive T lymphocytes was investigated using a baculovirus expression system. Insect cells expressing myristoylated Nef on their cell surface were shown to kill a proportion of CD4+ T cells within 8 h. However, N-terminal truncated and unmyristoylated Nef proteins were not present on the outer surface of insect cell membranes and failed to show any killing activity. Monoclonal antibodies against the C-terminal region of Nef inhibited cytolysis. Thus, we conclude that specific Nef-mediated cytolysis is induced by contact with unprimed CD4+ T lymphocytes without MHC restriction.
Fujii
Y
Y
Institute for Laboratory Animal Research, Nagoya University School of Medicine, Japan.
Otake
K
K
Tashiro
M
M
Adachi
A
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D015967:Gene Expression Regulation, Viral; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology*; D015752:Genes, env / Q000276:immunology; D015750:Genes, gag / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D018411:Spodoptera / Q000166:cytology; D014407:Tumor Cells, Cultured; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D011993:Recombinant Fusion Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus