AN ANTIBODY THAT BINDS THE IMMUNOGLOBULIN CDR3-LIKE REGION OF THE CD4MOLECULE INHIBITS PROVIRUS TRANSCRIPTION IN HIV-INFECTED T-CELLS

We used the polymerase chain reaction (PCR) to study which step(s) of the human immunodeficiency virus type 1 (HIV-1) life cycle may be bloc ked following treatment of HIV-exposed CEM cells with 13B8-2, a monocl onal antibody (mAb) specific for the immunoglobulin (Ig) CDR3-like reg ion of the CD4 molecule and able to inhibit the productive infection o f CEM cells by HIV-1. The presence of viral RNA was investigated and f ound in 13B8-2 mAb-treated CEM cells 30 min after viral exposure; the full-length viral DNA was found at 24 h post-infection. We also found integrated forms of viral DNA at 24 h post-infection. However, the int egrated provirus was transcriptionally inactive in 13B8-2 mAb-treated cells, as demonstrated by the absence of spliced HIV-1 mRNA. The lack of HiV transcription under 13B8-2 mAb treatment was confirmed by chlor amphenicol acetyltransferase (CAT) assay. We conclude that the inhibit ion of viral gene transcription accounts for the lack of progeny virio ns in culture supernatants of cells treated with this anti-CD4 mAb. We also demonstrate that 13B8-2 blocks viral production from chronically infected cells and restores CD4 cell-surface expression on CEM cells containing an integrated provirus(es). We found this effect to be reve rsible. Moreover, we demonstrate that 13B8-2 mAb treatment is efficien t on different HIV-1 and HIV-2 virus isolates. These results may have major implications for the treatment of AIDS.