Inhibition of human cytomegalovirus replication by overexpression of CREB1.
Antiviral Res
; 102: 11-22, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-24316029
ABSTRACT
Expression of the human cytomegalovirus (HCMV) major immediate-early (MIE) genes is regulated by a strong enhancer-containing promoter with multiple binding sites for various transcription factors, including cyclic AMP response element binding protein 1 (CREB1). Here we show that overexpression of CREB1 potently blocked MIE transcription and HCMV replication. Surprisingly, CREB1 still exhibited strong inhibition of the MIE promoter when all five CREB binding sites within the enhancer were mutated, suggesting that CREB1 regulated the MIE gene expression indirectly. Promoter deletion analysis and site-directed mutagenesis identified the region between -130 and -50 upstream of the transcription start site of the MIE gene as the "CREB1 responsive region". Mutations of SP1/3 and NF-κB binding sites within this region interrupted the inhibitory effect induced by CREB1 overexpression. Our findings suggest that overexpression of CREB1 can cause repression of HCMV replication and may contribute to the development of new anti-HCMV strategies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Replicación Viral
/
Expresión Génica
/
Proteína de Unión a Elemento de Respuesta al AMP Cíclico
/
Citomegalovirus
/
Interacciones Huésped-Patógeno
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Antiviral Res
Año:
2014
Tipo del documento:
Article
País de afiliación:
Singapur