An anti-CD4 (CDR3-loop) monoclonal antibody inhibits human immunodeficiency virus type 1 envelope glycoprotein-induced apoptosis.
Inhibition of human immunodeficiency virus type 1 (HIV-1)-inducing programmed cell death (PCD) by anti-CD4 monoclonal antibodies (mAbs) was investigated using DNA intercalant YOPRO-1 assay. We found that 13B8.2, an mAb that binds the CDR3-like loop in domain 1 (D1) of CD4, protected infected CEM cell cultures against HIV-1-induced PCD. Protection was not observed using another anti-CD4 mAb (BL4) that binds D1-D2, suggesting that the mechanism involved in cell protection against HIV-1-induced PCD requires engagement of precise CD4 epitopes. Because 13B8.2 is known to inhibit syncytia formation and virus transcription, this mAb could inhibit HIV-1-induced PCD by (1) inhibiting virus gene expression, (2) preventing viral envelope-CD4 interaction, and/or (3) interfering with apoptotic signals. Our data indicated that the absence of enhanced PCD in infected cell cultures treated with 13B8.2 mAb probably was the result of inhibition of HIV-1 replication and virus spread. Moreover, 13B8.2 mAb was found to inhibit PCD mediated by membrane-expressed HIV-1 envelope glycoproteins. Finally, we found that 13B8.2 mAb displayed no protective interference with apoptotic signal induced by Fas, dexamethasone, and serum withdrawal.
Guillerm
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Laboratoire Infections Rétrovirales et Signalisation Cellulaire, Institut de Biologie, CRBM/CNRS UPR 1086, 4 Boulevard Henri IV, Montpellier Cedex, 34060, France.
Robert-Hebmann
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Hibner
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Hirn
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Devaux
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D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D017209:Apoptosis; D015704:CD4 Antigens / Q000276:immunology*; D016895:Culture Media, Serum-Free; D003907:Dexamethasone / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000008:administration & dosage; D008562:Membrane Glycoproteins; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D019014:fas Receptor / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016895:Culture Media, Serum-Free; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D019014:fas Receptor; D003907:Dexamethasone