Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site.
J Gen Virol
; 94(Pt 7): 1528-1534, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23580428
ABSTRACT
Chronic viral hepatitis C is characterized by iron accumulation in the liver, and hepcidin regulates iron absorption. Hepatitis C virus (HCV) core+1/ARFP is a novel protein produced by a second functional ORF within the core gene. Here, using reporter assays and HCV bicistronic replicons, we show that, similarly to core, core+1/ARFP decreases hepcidin expression in hepatoma cells. The activator protein 1 (AP1) binding site of the human hepcidin promoter, shown here to be relevant to basal promoter activity and to the repression by core, is essential for the downregulation by core+1/ARFP while the previously described C/EBP (CCAAT/enhancer binding protein) and STAT (signal transducer and activator of transcription) sites are not. Consistently, expression of the AP1 components c-jun and c-fos obliterated the repressive effect of core and core+1/ARFP. In conclusion, we provide evidence that core+1/ARFP downregulates AP1-mediated transcription, providing new insights into the biological role of core+1/ARFP, as well as the transcriptional modulation of hepcidin, the main regulator of iron metabolism.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
/
Proteínas do Core Viral
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Hepacivirus
/
Fator de Transcrição AP-1
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Peptídeos Catiônicos Antimicrobianos
Limite:
Humans
Idioma:
En
Revista:
J Gen Virol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Grécia