SIGNALS TRANSDUCED THROUGH THE CD4 MOLECULE ON T-LYMPHOCYTES ACTIVATENF-KAPPA-B

We have demonstrated that native envelope glycoproteins of HIV-1, gp16 0 can induce activation of the transcription factor, NF-kappa B. The s timulatory effects of gp160 are mediated through the CD4 molecule, sin ce pretreatment with soluble CD4 abrogates its activity. The gp160-ind uced NF-kappa B complex consists of p65, p50 and c-rel proteins. The s timulatory effect of gp160 on NF-kappa B activation is protein synthes is independent, is dependent upon protein tyrosine phosphorylation, an d abrogated by inhibitors of protein kinase C. The gp160-mediated acti vation of NF-kappa B in CD4 positive T cells may be involved in biolog ical effects, e.g.,enhanced HIV replication, hypergammaglobulinemia, i ncreased cytokine secretion, hypercellularity in bone marrow and apopt osis. (C) 1994 Academic Press, Inc.