Soluble Nef antigen of HIV-1 is cytotoxic for human CD4+ T cells.

We have previously shown that Nef-gene 10 fusion protein induces marked growth arrest of human primary CD4+ T cells. Here, in vitro cytostatic and cytotoxic activities of human immunodeficiency virus type 1 (HIV-1) Nef against CD4+ T cells were extensively investigated. Growth of human CD4+ cells was inhibited significantly just by the addition of purified full-length Nef to cultures. When Nef was cross-linked by anti-Nef antibodies, it became very cytocidal for CD4+ T cells. A high percentage of sera from HIV-1-infected individuals contained soluble Nef. Thus, soluble Nef in vivo may play an important role in immunodysfunction of CD4+ T lymphocytes in HIV-1 infection.