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.

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; Claudia, Montaldo; Laura, Santangelo; Cristina Di, Giacomo; Viviana, Costa; Amicone, Laura; Giuseppe, Ippolito; Leopoldo Paolo, Pucillo; Tonino, Alonzi; Tripodi, Marco. - In: JOURNAL OF PROTEOME RESEARCH. - ISSN 1535-3893. - ELETTRONICO. - 11:5(2012), pp. 2786-2797. [10.1021/pr201128s]

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;AMICONE, Laura;TRIPODI, Marco
2012

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.
2012
Hcv infection; hypobetalipoproteinemia; iron metabolism; liver steatosis
01 Pubblicazione su rivista::01a Articolo in rivista
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; Claudia, Montaldo; Laura, Santangelo; Cristina Di, Giacomo; Viviana, Costa; Amicone, Laura; Giuseppe, Ippolito; Leopoldo Paolo, Pucillo; Tonino, Alonzi; Tripodi, Marco. - In: JOURNAL OF PROTEOME RESEARCH. - ISSN 1535-3893. - ELETTRONICO. - 11:5(2012), pp. 2786-2797. [10.1021/pr201128s]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/440830
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