INTERFERON INDUCTION BY HIV GLYCOPROTEIN-120 - ROLE OF THE V3 LOOP

We have studied the mechanism of IFN induction by HIV-1 in peripheral blood mononuclear cells (PBMC), using recombinant viral membrane glyco proteins as potential inducers. Whereas 8 nM HIVIIIB-derived gp120 res ulted in IFN levels between 80 and 2000 IU/ml with PBMC from different donors, gp120 from the MN strain was not an inducer. Preincubation of HIVIIIB-gp120 with a monoclonal antibody (mAB) to its CD4 binding dom ain or of PBMC with a mAB to the gp120 binding domain of CD4 abolished IFN induction. Antibodies against the third extracellular domain of C D4 which did not block binding of gp120, however, were also inhibitory . Furthermore, several mABs to the third variable loop (V3) of HIVIIIB -gp120 also blocked IFN induction, suggesting an important role of V3 in this process. This was further supported by the inhibitory action o f peptides homologous to complete or partial sequences of V3. We concl ude that after binding of gp120 to its CD4 receptor the vs loop can be positioned close to the membrane of the responder cells by bending of gp120-occupied CD4 at its hinge region between extracellular domains 2 and 3. As a result vs is able to interact with a vs-specific ''secon dary receptor'' on the membranes of these cells. We suggest that it is the latter interaction which triggers IFN induction. (C) 1994 academi c Press, Inc.