MULTIPLE EFFECTS OF CD4 CDR3-RELATED PEPTIDE DERIVATIVES SHOWING ANTI-HIV-1 ACTIVITY ON HIV-1 GP120 FUNCTIONS

The interaction of the human immunodeficiency virus type 1 (HIV-1) env elope glycoprotein gp120 with CD4 CDR3-related peptide derivatives sho wing anti-HIV-1 activity has been studied. Conformational changes in g p120, which could affect its interaction with CD4 and its shedding fro m virions, were detected by fluorescence spectrum analysis of tryptoph an residues after addition of peptide representative of the CD4 CDR3-r elated region, but not the CD4 CDR2-related region. Interestingly, the addition of scrambled peptide, S1 (with altered amino acid sequence c ompared with the native CDR3-related peptide but unaltered overall com position), which we recently showed to have stronger anti-HIV-1 activi ty than the original CDR3-related peptide, had no effects on the confo rmational change in gp120 or on its interaction with CD4 and its shedd ing from HIV-1 virions. However, all of the CDR3-related peptides, inc luding S1, showed blocking effects on the binding of antibodies agains t gp120 V3 loop and C-terminus regions. Thus, we concluded that there were at least two separable activities of the CDR3-related peptides in anti-HIV-1 activity, i.e. induction of conformational changes in gp12 0, which could affect its binding to CD4 and to gp41 (as observed in n ative CDR3-related peptides), and inactivation of V3 loop and C-termin us regions in gp120 (as observed in all of the CDR3-related peptides, including S1).