1887

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Volume 94, Issue 7

Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site Free

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.

  • Received:
  • Accepted:
  • Published Online:
© 2013 SGM
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2013-07-01
2023-09-27
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Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site
J. Gen. Virol. 94, 1528 (2013); https://doi.org/10.1099/vir.0.050328-0
/content/journal/jgv/10.1099/vir.0.050328-0
/content/journal/jgv/10.1099/vir.0.050328-0
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