An antibody that binds the immunoglobulin CDR3-like region of the CD4 molecule 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 blocked following treatment of HIV-exposed CEM cells with 13B8-2, a monoclonal antibody (mAb) specific for the immunoglobulin (Ig) CDR3-like region of the CD4 molecule and able to inhibit the productive infection of CEM cells by HIV-1. The presence of viral RNA was investigated and found 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 integrated 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 chloramphenicol acetyltransferase (CAT) assay. We conclude that the inhibition of viral gene transcription accounts for the lack of progeny virions 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 reversible. Moreover, we demonstrate that 13B8-2 mAb treatment is efficient on different HIV-1 and HIV-2 virus isolates. These results may have major implications for the treatment of AIDS.
Benkirane
M
M
CRBM-UPR 9008 du CNRS et INSERM U249, Centre de Tri des Molécules anti-HIV, Montpellier, France.
Corbeau
P
P
Housset
V
V
Devaux
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000254:growth & development*; D015498:HIV-2 / Q000235:genetics / Q000254:growth & development; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D017931:DNA Primers; D004279:DNA, Viral; D012367:RNA, Viral; D015375:Receptors, Interleukin-2; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase