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 journalArticle

12 Citations (Scopus)

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

Fingerprint

Apoferritins
Apolipoprotein B-100
Virus Diseases
Viruses
Hepacivirus
Fatty Liver
Liver
Proteasome Endopeptidase Complex
Ferritins
Computational Biology
Cell culture
Proteomics
Small Interfering RNA
Lipoproteins
Antiviral Agents
Up-Regulation
Down-Regulation
Cell Culture Techniques
Fats
Plasmas

Keywords

  • HCV infection
  • hypobetalipoproteinemia
  • iron metabolism
  • liver steatosis

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Ferritin heavy chain is the host factor responsible for HCV-induced inhibition of apoB-100 production and is required for efficient viral infection. / Mancone, Carmine; Montaldo, Claudia; Santangelo, Laura; Di Giacomo, Cristina; Costa, Viviana; Amicone, Laura; Ippolito, Giuseppe; Pucillo, Leopoldo Paolo; Alonzi, Tonino; Tripodi, Marco.

In: Journal of Proteome Research, Vol. 11, No. 5, 04.05.2012, p. 2786-2797.

Research output: Contribution to journalArticle

Mancone, Carmine ; Montaldo, Claudia ; Santangelo, Laura ; Di Giacomo, Cristina ; Costa, Viviana ; Amicone, Laura ; Ippolito, Giuseppe ; Pucillo, Leopoldo Paolo ; Alonzi, Tonino ; Tripodi, Marco. / Ferritin heavy chain is the host factor responsible for HCV-induced inhibition of apoB-100 production and is required for efficient viral infection. In: Journal of Proteome Research. 2012 ; Vol. 11, No. 5. pp. 2786-2797.
@article{6a0ceef9b07f4c80afaf9420cc604f69,
title = "Ferritin heavy chain is the host factor responsible for HCV-induced inhibition of apoB-100 production and is required for efficient viral infection",
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.",
keywords = "HCV infection, hypobetalipoproteinemia, iron metabolism, liver steatosis",
author = "Carmine Mancone and Claudia Montaldo and Laura Santangelo and {Di Giacomo}, Cristina and Viviana Costa and Laura Amicone and Giuseppe Ippolito and Pucillo, {Leopoldo Paolo} and Tonino Alonzi and Marco Tripodi",
year = "2012",
month = "5",
day = "4",
doi = "10.1021/pr201128s",
language = "English",
volume = "11",
pages = "2786--2797",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "5",

}

TY - JOUR

T1 - Ferritin heavy chain is the host factor responsible for HCV-induced inhibition of apoB-100 production and is required for efficient viral infection

AU - Mancone, Carmine

AU - Montaldo, Claudia

AU - Santangelo, Laura

AU - Di Giacomo, Cristina

AU - Costa, Viviana

AU - Amicone, Laura

AU - Ippolito, Giuseppe

AU - Pucillo, Leopoldo Paolo

AU - Alonzi, Tonino

AU - Tripodi, Marco

PY - 2012/5/4

Y1 - 2012/5/4

N2 - 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.

AB - 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.

KW - HCV infection

KW - hypobetalipoproteinemia

KW - iron metabolism

KW - liver steatosis

UR - http://www.scopus.com/inward/record.url?scp=84860605911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860605911&partnerID=8YFLogxK

U2 - 10.1021/pr201128s

DO - 10.1021/pr201128s

M3 - Article

C2 - 22443280

AN - SCOPUS:84860605911

VL - 11

SP - 2786

EP - 2797

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 5

ER -