Evidence of HIV type 1 glycoprotein 120 binding to recombinant N-methyl-D-aspartate receptor subunits expressed in a baculovirus system

Activation of the N-methyl-D-aspartate (NMDA) receptor by HIV-1 envelope gl ycoprotein 120 (gp120) is thought to represent at least one of the pathways causing neuronal damage in AIDS patients. In the present study, recombinan t gp120 binding to NMDA receptor subunits expressed in a baculovirus system was examined by immunocytochemistry and a binding assay, using horseradish peroxidase (HRP)-conjugated and I-125-labeled recombinant gp120, respectiv ely. We found that recombinant gp120 binds to Sf21 cells expressing epsilon 1/zeta 1 or epsilon 2/zeta 1 combined NMDA receptor subunits, but not to S f21 cells infected with mock virus or Sf21 cells expressing a single epsilo n 1, epsilon 2, or zeta 1 NMDA receptor subunit, The binding was strongly b locked by unlabeled recombinant gp120, monoclonal anti-HIV-1 gp160 antibody , and a mixture of anti-epsilon 1/epsilon 2 and anti-zeta 1 antibodies. The same results were obtained by flow cytometric analysis. These data suggest that HIV-1 gp120 may directly bind to the NMDA receptor. This evidence enh ances our understanding of the mechanism of HIV-1-induced neuronal damage i n AIDS patients.