AEGiS-15IAC: Cell cycle arrest in G2 induces HIV-1 transcriptional activation through histone acetylation and recruitment of CBP, NF-kB and c-Jun to the LTR promoter.

15th International AIDS Conference


Bangkok, Thailand - July 11-16, 2004

DonateNow
Print this article

Cell cycle arrest in G2 induces HIV-1 transcriptional activation through histone acetylation and recruitment of CBP, NF-kB and c-Jun to the LTR promoter.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1398)

Thierry SG, Marechal V, Rosenzwajg M, Nicolas JC, Gozlan J
UMR 7079, Universite Pierre et Marie Curie, Paris, France

BACKGROUND: In HIV-1 infected cells, a cell cycle arrest in G2, notably induced by the viral protein Vpr, increases viral expression and may represent a strategy for the virus to optimise its expression. In latently infected cells, balance between viral silencing and reactivation relies on the nucleosomal organization of the integrated LTR. We analysed the modifications of the nucleosome nuc-1, located downstream the TATA box, in chronically infected T cells upon G2 arrest.

METHODS: ACH-2 cells were arrested in G2 by several drugs. HIV-1 expression was quantified by RT-PCR and p24 antigen release in cell supernatants. Histone acetylation, binding of nuclear factors and recruitment of co-activators at nuc-1 was quantified by chromatin immunoprecipitation assay, followed by a real time PCR around the sequence of the nucleosome nuc-1.

RESULTS: Histone H3 and H4 of nuc-1 are specifically hyperacetylated during the G2 arrest. This modification is associated with an increased LTR-driven transcription. nuc-1 hyperacetylation also associated with the recruitment of histone acetyl transferase CBP, NF-kB and c-Jun. NF-kB and/or c-Jun binding in G2 arrested cells appeared to be required for CBP recruitment, as well as for nuc-1 remodelling and viral reactivation

CONCLUSIONS: A G2 arrest induces specific modifications at the nucleosome nuc-1 in the integrated LTR that leads to HIV-1 reactivation.

Keywords: AEGIS, Trans-Activation (Genetics), Nuclear Proteins, Trans-Activators, Promoter Regions (Genetics), Terminal Repeat Sequences, NF-kappa B, Proto-Oncogene Proteins c-jun, HIV-1, Genes, jun, Histones, Chromatin, Nucleosomes, Cell Cycle, Transcription, Genetic, CREB-binding protein, genetics

040711
ThOrA1398

Copyright © 2004 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.