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 I (DI) of CD4, protected infected CEM cell cultures against HIV-1-induced PCD. Protection was not observed using another anti-CD4 mAb (BL4) that hinds D1-D2, suggesting that the mechanism involved in cell protection against HIV-1-induced PGD requires engagement of precise CD4 epitopes. Because 13B8.2 is known to inhibit syncytia formation and virus transcription, this mAb could inhibit HIV-I-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-I envelope glycoproteins. Finally, we found that 13B8.2 mAb displayed no protective interference with apoptotic signal induced by Fas, dexamethasone, and serum withdrawal. (C) 1998 Academic Press.