Ferritin heavy chain is the host factor responsible for HCV-induced inhibition of apoB-100 production and is required for efficient viral infection

Carmine Mancone, Claudia Montaldo, Laura Santangelo, Cristina Di Giacomo, Viviana Costa, Laura Amicone, Giuseppe Ippolito, Leopoldo Paolo Pucillo, Tonino Alonzi, Marco Tripodi

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatic fat export occurs by apolipoprotein B-100-containing lipoprotein production, whereas impaired production leads to liver steatosis. Hepatitis C virus (HCV) infection is associated to dysregulation of apoB-100 secretion and steatosis; however, the molecular mechanism by which HCV affects the apoB-100 secretion is not understood. Here, combining quantitative proteomics and computational biology, we propose ferritin heavy chain (Fth) as being the cellular determinant of apoB-100 production inhibition. By means of molecular analyses, we found that HCV nonstructural proteins and NS5A appear to be sufficient for inducing Fth up-regulation. Fth in turn was found to inhibit apoB-100 secretion leading to increased intracellular degradation via proteasome. Notably, intracellular Fth down-regulation by siRNA restores apoB-100 secretion. The inverse correlation between ferritin and plasma apoB-100 concentrations was also found in JFH-1 HCV cell culture systems (HCVcc) and HCV-infected patients. Finally, Fth expression was found to be required for robust HCV infection. These observations provide a further molecular explanation for the onset of liver steatosis and allow for hypothesizing on new therapeutic and antiviral strategies.

Original languageEnglish
Pages (from-to)2786-2797
Number of pages12
JournalJournal of Proteome Research
Volume11
Issue number5
DOIs
Publication statusPublished - May 4 2012

Keywords

  • HCV infection
  • hypobetalipoproteinemia
  • iron metabolism
  • liver steatosis

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Fingerprint Dive into the research topics of 'Ferritin heavy chain is the host factor responsible for HCV-induced inhibition of apoB-100 production and is required for efficient viral infection'. Together they form a unique fingerprint.

Cite this