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 pro grammed 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, protect ed infected CEM cell cultures against HIV-1-induced PCD. Protection wa s not observed using another anti-CD4 mAb (BL4) that hinds D1-D2, sugg esting that the mechanism involved in cell protection against HIV-1-in duced PGD requires engagement of precise CD4 epitopes. Because 13B8.2 is known to inhibit syncytia formation and virus transcription, this m Ab could inhibit HIV-I-induced PCD by (1) inhibiting virus gene expres sion, (2] preventing Viral envelope-CD4 interaction, and/or (3) interf ering with apoptotic signals. Our data indicated that the absence of e nhanced PCD in infected cell cultures treated with 13B8.2 mAb probably was the result of inhibition of HIV-1 replication and virus spread. M oreover, 13B8.2 mAb was found to inhibit PCD mediated by membrane-expr essed 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.