Histone deacetylase mediated transcriptional activation reduces proviral loads in HTLV-1 associated myelopathy/tropical spastic paraparesis patients.
Blood
; 110(10): 3722-8, 2007 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-17717136
ABSTRACT
Epigenetic modifications of chromatin may play a role in maintaining viral latency and thus persistence of the human T-lymphotropic virus type 1 (HTLV-1), which is responsible for HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A major determinant of disease progression is increased peripheral blood proviral load (PVL), possibly via the accumulation of infected cells in the central nervous system (CNS) creating a damaging inflammatory response. Current therapeutic approaches that focus on reducing either cell proliferation, viral replication, or tissue invasion are still unsatisfactory. Contrasting with these inhibitory strategies, we evaluated the efficacy of a novel approach aimed, paradoxically, at activating viral gene expression to expose virus-positive cells to the host immune response. We used valproate (VPA), a histone deacetylase inhibitor that has been used for decades as a chronic, safe treatment for epileptic disorders. Based on in vitro and in vivo data, we provide evidence that transient activation of the latent viral reservoir causes its collapse, a process that may alleviate the condition of HAM/TSP. This represents the first such approach to treating HAM/TSP, using gene activation therapy to tilt the host-pathogen balance in favor of an existing antiviral response. This trial is registered at http//clinicaltrials.gov/as no. NCT00519181.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus Linfotrópico T Tipo 1 Humano
/
Paraparesia Espástica Tropical
/
Ativação Transcricional
/
Provírus
/
Carga Viral
/
Histona Desacetilases
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
França