The Catalytic Activity of Protein Disulfide Isomerase Is Involved in Human Immunodeficiency Virus Envelope-Mediated Membrane Fusion After CD4 Cell Binding

J Infect Dis. 2001 Mar 1;183(5):744-52. doi: 10.1086/318823. Epub 2001 Jan 25.

Abstract

Protein disulfide isomerase (PDI) is a multifunctional protein with thiol-disulfide redox-isomerase activities. It catalyzes thiol-disulfide interchange reactions on the cell surface that may cause structural modifications of exofacial proteins. PDI inhibitors alter human immunodeficiency virus (HIV) spread, and it has been suggested that PDI may be necessary to trigger HIV entry. This study examined this hypothesis by using cell-to-cell fusion assays, in which the HIV envelope (Env) expressed on the cell surface interacts with CD4(+) lymphocytes. PDI is clustered at the lymphocyte surface in the vicinity of CD4-enriched regions, but both antigens essentially do not colocalize. Anti-PDI antibodies and 2 inhibitors of its catalytic function altered Env-mediated membrane fusion at a post-CD4 cell binding step. The fact that the PDI catalytic activity present on lymphocytes is required for fusion supports the hypothesis that catalysts assist post-CD4 cell binding conformational changes within Env.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / enzymology*
  • CD4-Positive T-Lymphocytes / ultrastructure
  • CD4-Positive T-Lymphocytes / virology
  • Cell Aggregation
  • Cells, Cultured
  • Dithionitrobenzoic Acid / pharmacology
  • HIV / physiology*
  • HIV / ultrastructure
  • HIV Infections / etiology*
  • Membrane Fusion / immunology
  • Membrane Fusion / physiology*
  • Microscopy, Confocal
  • Oxidation-Reduction
  • Protein Disulfide-Isomerases / antagonists & inhibitors
  • Protein Disulfide-Isomerases / metabolism*
  • Sulfhydryl Reagents / pharmacology
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / physiology*

Substances

  • Sulfhydryl Reagents
  • Viral Envelope Proteins
  • Dithionitrobenzoic Acid
  • Protein Disulfide-Isomerases