Human immunodeficiency virus type 1 Nef protein on the cell surface is cytocidal for human CD4+ T cells.
We have previously shown that the carboxyl-terminal region of human immunodeficiency virus type 1 (HIV-1) Nef antigen present on the outer surface of virus-infected cells has affinity for uninfected T cells. Here, the in vitro cytotoxic potential of HIV-1 Nef on the T cell surface against CD4+ T cells was investigated in detail. Human T cells expressing Nef on the cell surface by transfection with non-infectious mutant HIV-1 proviruses were demonstrated to kill CD4+ T cells efficiently. Furthermore, it was shown that the carboxyl-terminal portion of Nef was cytotoxic for CD4+ T cells and that monoclonal antibody against the carboxyl-terminal region of Nef inhibited Nef induced-cytolysis. Thus, we concluded that Nef protein on CD4+ T cells may play an important role in the specific loss of CD4+ T lymphocytes during HIV-1 infection.
Fujii
Y
Y
Institute for Laboratory Animal Research, Nagoya University School of Medicine, Japan.
Otake
K
K
Tashiro
M
M
Adachi
A
A
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane; D003601:Cytotoxicity Tests, Immunologic; D003603:Cytotoxins / Q000235:genetics / Q000633:toxicity; D015693:Gene Products, nef / Q000235:genetics / Q000633:toxicity*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009154:Mutation; D013329:Structure-Activity Relationship; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus
D003603:Cytotoxins; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus