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

Emmanuel Fenouillet (1) , Rym Barbouche , Joël Courageot (2) , Raymond Miquelis (3)

1 NICN - Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN
2 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
3 IP - Ingénierie des protéines

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

Domaines: Sciences du Vivant [q-bio]; Biochimie [q-bio.BM]; Interactions cellulaires [q-bio.CB]

Emmanuel Fenouillet, Rym Barbouche, Joël Courageot, Raymond Miquelis. The Catalytic Activity of Protein Disulfide Isomerase Is Involved in Human Immunodeficiency Virus Envelope–Mediated Membrane Fusion after CD4 Cell Binding. Journal of Infectious Diseases, 2001, 183 (5), pp.744-752. ⟨10.1086/318823⟩. ⟨hal-03872326⟩