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.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Mancone C,Montaldo C,Santangelo L,Di Giacomo C,Costa V,Amicone L,Ippolito G,Pucillo LP,Alonzi T,Tripodi Mdoi
10.1021/pr201128ssubject
Has Abstractpub_date
2012-05-04 00:00:00pages
2786-97issue
5eissn
1535-3893issn
1535-3907journal_volume
11pub_type
杂志文章abstract：:Although the legume-rhizobium symbiosis is a most-important biological process, there is a limited knowledge about the protein interaction network between host and symbiont. Using interolog- and domain-based approaches, we constructed an interspecies protein interactome containing 5115 protein-protein interactions bet...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.8b00209
更新日期：2018-09-07 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.6b00383
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journal_title：Journal of proteome research
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journal_title：Journal of proteome research
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr2012279
更新日期：2012-04-06 00:00:00
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journal_title：Journal of proteome research
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journal_title：Journal of proteome research
pub_type： 杂志文章
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr0601943
更新日期：2007-01-01 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.5b00772
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journal_title：Journal of proteome research
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pub_type： 杂志文章
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更新日期：2021-01-27 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.9b00258
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journal_title：Journal of proteome research
pub_type： 杂志文章
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journal_title：Journal of proteome research
pub_type： 杂志文章
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更新日期：2012-09-07 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
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journal_title：Journal of proteome research
pub_type： 信件
doi：10.1021/pr049935v
更新日期：2004-09-01 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr050148n
更新日期：2005-11-01 00:00:00
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journal_title：Journal of proteome research
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journal_title：Journal of proteome research
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journal_title：Journal of proteome research
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journal_title：Journal of proteome research
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journal_title：Journal of proteome research
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更新日期：2011-10-07 00:00:00
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journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.6b00772
更新日期：2016-11-04 00:00:00
