The synthetic CD4 exocyclic CDR3.AME(82-89) inhibits NF-kappaB nuclear translocation, HIV-1 promoter activation, and viral gene expression.
We have previously shown that the synthetic aromatically modified exocyclic (AME) analog (CDR3.AME(82-89), derived from the CDR3 (residues 82-89) region of CD4 domain 1, inhibits replication of human immunodeficiency virus type 1 (HIV-1) in infected cells. In this work, we investigated the mechanism by which this inhibition is achieved. Although cells exposed to HIV-1 and treated with the CDR3.AME(82-89) peptide did not release viral particles for more than a week and kept surface expression of CD4, viral DNA was found in those cells 24 h after virus exposure, indicating that the CDR3.AME(82-89) analog does not prevent virus entry. However, virus transcription remained extremely low in infected cells, as demonstrated by the study of spliced HIV-1 mRNA in cultures treated with CDR3.AME(82-89) 72 h postinfection. Finally, the CDR3.AME(82-89) peptide was found to be a potent inhibitor of HIV-1 promoter activity and nuclear factor-kappaB translocation, indicating that the antiviral property of this peptide is, at least in part, linked with the ability of the molecule to prevent HIV-1 transcription.
Roland
J
J
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS EP J0004, Institut de Biologie, Montpellier, France.
Berezov
A
A
Greene
M I
MI
Murali
R
R
Piatier-Tonneau
D
D
Devaux
C
C
Briant
L
L
D019380:Anti-HIV Agents / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; C402366:CDR3.AME(82-89); D016328:NF-kappa B; D010446:Peptide Fragments; D010456:Peptides, Cyclic