The catalytic activity of protein disulfide isomerase is involved in humanimmunodeficiency virus envelope- mediated membrane fusion after CD4 cell binding

Protein disulfide isomerase (PDI) is a multifunctional protein with thiol-d isulfide redox-isomerase activities. It catalyzes thiol-disulfide interchan ge 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 HI V entry. This study examined this hypothesis by using cell-to-cell fusion a ssays, in which the HIV envelope (Env) expressed on the cell surface intera cts 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 f act 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.