INTERACTION OF HIV-1 GP120 MOLECULE FRAGMENTS WITH HUMAN MONOCYTES - DIFFERENT REQUIREMENTS FOR TUMOR-NECROSIS-FACTOR-ALPHA AND IL-6 PRODUCTION

The HIV-1 gp120 recombinant protein fragment eneompassing aa residues 410-511, that contains the CD4 binding region (rp120cd), and fragment aa 446-511, which lacks the sequence responsible for CD4 binding (rp12 0), were synthesized to study their ability to induce TNF synthesis in human monocytes. The rp120cd stimulated TNF alpha secretion by monocy tes while the rp120 and full-length recombinant protein (FL gp120), us ed as control, failed to do so. However, FL gp120 stimulated periphera l blood mononuclear cells (PBMC) and lymphocytes for TNF production an d this was inhibited by anti-CD4 MAb. The rp120cd also caused TNF secr etion by PBMC that was not blocked by this antibody. Furthermore, FL g p120 but not rp120cd inhibited anti-CD4 mAb binding to CEM cells. Henc e, FL gp120 may cause TNF release from lymphocytes by binding to CD4, while rp120cd interacts with monocytes but not lymphocytes and induces TNF production by a mechanism not involving CD4 binding. Unexpectedly , FL gp120 but not rpl20cd stimulated IL-6 secretion and IL-6 mRNA syn thesis in monocytes. The FL gp120-induced production of IL-6 by monocy tes was inhibited by anti-CD4 monoclonal antibody (MAb). Thus, there m ay be different requirements for TNF induction in lymphocytes and mono cytes stimulated with various preparations of gp120 and for the select ive induction of cytokines in monocytes. The enhanced production of TN F in HIV infection and AIDS may involve distinct cellular sources acid different mechanisms. (C) 1995 Academic Press, Inc.