Multi-Branched Peptide Constructs (MBPC) of the V3 Loop of Envelope Glycoprotein gp120 Inhibit Human Immunodeficiency Virus-Induced Syncytium Formation

Abstract

The principle neutralizing domain of human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein, the V3 region, is likely to be involved in HIV-mediated membrane fusion. While V3-derived monomeric peptides enhance HIV-1 infection through a CD4-dependent mechanism (DeRossi et al., 1991), the authors observed that multi-branched peptide constructs (MBPC) based on the V3 consensus sequence of European/North American isolates inhibited both HIV-1 and HIV-2 mediated syncytia at concentrations that did not alter cell viability nor blood lymphocyte allogeneic, antigen- or mitogen-induced proliferations. V3 MBPC bound to CD4+ cells and their binding was inhibited by soluble CD4 and by a benzylated peptide derived from its CDR3 region. These data indicate that V3-based MBPC may be used for delineating HIV entry mechanisms and might behave as antiviral agents of broad specificity.