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

Ioly Kotta-Loizou, Niki Vassilaki, George Pissas, Athanassios Kakkanas, Latifa Bakiri, Ralf Bartenschlager, Penelope Mavromara

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1528-1534
Number of pages7
JournalJournal of General Virology
Volume94
Issue numberPt 7
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Keywords

  • Anti-Bacterial Agents/metabolism
  • Antimicrobial Cationic Peptides/metabolism
  • Binding Sites
  • Cell Line, Tumor
  • Down-Regulation
  • Hepacivirus/pathogenicity
  • Hepcidins
  • Humans
  • Iron/metabolism
  • Liver/cytology
  • Promoter Regions, Genetic
  • Transcription Factor AP-1/chemistry
  • Transcriptional Activation
  • Viral Core Proteins/genetics

Fingerprint

Dive into the research topics of 'Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site'. Together they form a unique fingerprint.

Cite this