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.
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, Institut de Biologie, CRBM/CNRS UPR 1086, 4 Boulevard Henri IV, Montpellier Cedex, 34060, France.
C
C
Guillerm
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V
Robert-Hebmann
U
U
Hibner
M
M
Hirn
C
C
Devaux
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