Signals Transduced through the CD4 Molecule on T-Lymphocytes Activate NF-κB

Abstract

We have demonstrated that native envelope glycoproteins of HIV-1, gp160 can induce activation of the transcription factor, NF-κB. The stimulatory effects of gp160 are mediated through the CD4 molecule, since pretreatment with soluble CD4 abrogates its activity. The gp160-induced NF-κB complex consists of p65, p50 and c-rel proteins. The stimulatory effect of gp160 on NF-κB activation is protein synthesis independent, is dependent upon protein tyrosine phosphorylation, and abrogated by inhibitors of protein kinase C. The gp160-mediated activation of NF-κB in CD4 positive T cells may be involved in biological effects, e.g., enhanced HIV replication, hypergammaglobulinemia, increased cytokine secretion, hypercellularity in bone marrow and apoptosis. © 1994 Academic Press, Inc.