Histone deacetylase inhibitor Scriptaid reactivates latent HIV-1 promoter by inducing histone modification in in vitro latency cell lines.
Int J Mol Med
; 26(2): 265-72, 2010 Aug.
Article
en En
| MEDLINE
| ID: mdl-20596607
ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) latency remains a major problem for the eradication of viruses in infected individuals undergoing highly active anti-retroviral therapy. By inhibiting HIV-1 gene expression and virus production, histone deacetylase (HDAC) may contribute to the quiescence of HIV-1 within resting CD4+ T cells. A novel HDAC inhibitor, Scriptaid, has been found to have robust activity and lower toxicity compared to trichostatin A (TSA). We therefore investigated Scriptaid for its capability to reverse HIV-1 latency by inducing HIV-1 activation in the Jurkat T cell line containing latent HIV proviruses. We found that Scriptaid can activate HIV-1 gene expression in these latent infected cells by 2-15-fold over background levels, as analyzed by flow cytometry. Chromatin immunoprecipitation (ChIP) assays further revealed that the Scriptaid increased the acetylation level of histones H3 and H4 at the nucleosome 1 site of the HIV-1 long terminal repeat compared to mock treatment. In addition, Scriptaid can synergize with prostratin or tumor necrosis factor-alpha to activate the HIV-1 promoter, with relatively lower toxicity compared to TSA. These studies suggest the potential of Scriptaid in anti-latency therapies.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinolinas
/
VIH-1
/
Regiones Promotoras Genéticas
/
Latencia del Virus
/
Epigénesis Genética
/
Inhibidores de Histona Desacetilasas
/
Hidroxilaminas
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2010
Tipo del documento:
Article