Bathophenanthroline disulfonate and soluble CD4 as probes for early events of HIV type 1 entry. Academic Article uri icon

Overview

abstract

  • We report here that a metalloprotease inhibitor, bathophenanthroline disulfonate (Bphe-ds), neutralizes both laboratory-adapted and primary strains of HIV-1. Presaturation of Bphe-ds with zinc does not alter its neutralizing activity, suggesting that the metal-chelating ability of Bphe-ds is not required for neutralization. Bphe-ds blocks infection of CD4+ cells at the stage of viral entry, not through a direct viricidal effect, but by interfering with both binding and postbinding events. This drug interacts with HIV-1 envelope, blocking almost completely the binding of three MAbs that recognize epitopes overlapping the CD4-binding site on gp120, but has no effect on the binding of MAbs directed to the cellular receptor CD4. The exposure of epitopes in the V2 and V3 but not C5 domains of gp120 is partially decreased in the presence of Bphe-ds, suggesting that the drug induces conformational changes in the envelope glycoprotein(s). Binding of both virions and soluble gp120 to CD4+ cells is inhibited by this drug in a dose-dependent manner. This contrasted with the effects of soluble CD4, which actually increased binding of virions to cells at 4 degrees C, while inhibiting the binding of soluble gp120. Bphe-ds also increases shedding of gp120 from cells infected with HIV-1IIIB. Thus, Bphe-ds appears to be an envelope-directed inhibitor of HIV-1 that neutralizes HIV-1 infectivity via multiple mechanisms.

publication date

  • January 1, 1995

Research

keywords

  • CD4 Antigens
  • CD4-Positive T-Lymphocytes
  • HIV Envelope Protein gp120
  • HIV-1
  • Phenanthrolines

Identity

Scopus Document Identifier

  • 0029021507

Digital Object Identifier (DOI)

  • 10.1089/aid.1995.11.127

PubMed ID

  • 7734186

Additional Document Info

volume

  • 11

issue

  • 1