{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:17:35Z","timestamp":1789975055120,"version":"4.0.1"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2015,4,13]],"date-time":"2015-04-13T00:00:00Z","timestamp":1428883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0123190","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T18:56:19Z","timestamp":1429124179000},"page":"e0123190","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Roles of Endoplasmic Reticulum Overload Response Induced by HCV and NS4B Protein in Human Hepatocyte Viability and Virus Replication"],"prefix":"10.1371","volume":"10","author":[{"given":"Lingbao","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruina","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunli","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,4,13]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.virol.2009.06.039","article-title":"Hepatitis C virus NS4B induces unfolded protein response and endoplasmic reticulum overload response-dependent NF-kappaB activation","volume":"391","author":"S Li","year":"2009","journal-title":"Virology"},{"key":"ref2","unstructured":"Li S, Kong L, Yu X (2013) The expanding roles of endoplasmic reticulum stress in virus replication and pathogenesis. Crit Rev Microbiol: 1\u201315."},{"key":"ref3","doi-asserted-by":"crossref","first-page":"9294","DOI":"10.1073\/pnas.0503596102","article-title":"Robust hepatitis C virus infection in vitro","volume":"102","author":"J Zhong","year":"2005","journal-title":"Proc Natl Acas Sci U S A"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"40778","DOI":"10.1074\/jbc.M303248200","article-title":"Hepatitis C virus NS5A and subgenomic replicon activate NF-kappaB via tyrosine phosphorylation of IkappaBalpha and its degradation by calpain protease","volume":"278","author":"G Waris","year":"2003","journal-title":"J Biol Chem"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/j.bcp.2006.06.029","article-title":"Inflammation and cancer: How hot is the link?","volume":"72","author":"BB Aggarwal","year":"2006","journal-title":"Biochem Pharmacol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1586\/ern.10.21","article-title":"NF-\u03baB and STAT3 signaling in glioma: targets for future therapies","volume":"10","author":"GP Atkinson","year":"2010","journal-title":"Expert Rev Neurother"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"4465","DOI":"10.1158\/1078-0432.CCR-13-0080","article-title":"Nimbolide, a Limonoid Triterpene, Inhibits Growth of Human Colorectal Cancer Xenografts by Suppressing the Proinflammatory Microenvironment","volume":"19","author":"SC Gupta","year":"2013","journal-title":"Clin Cancer Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/hep.21802","article-title":"Nuclear factor-\u03baB and the hepatic inflammation-fibrosis-cancer axis","volume":"46","author":"AM Elsharkawy","year":"2007","journal-title":"Hepatology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/nature04077","article-title":"Unravelling hepatitis C virus replication from genome to function","volume":"436","author":"BD Lindenbach","year":"2005","journal-title":"Nature"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/hep.22715","article-title":"CD56+ T cells inhibit hepatitis C virus replication in human hepatocytes","volume":"49","author":"L Ye","year":"2009","journal-title":"Hepatology"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"40778","DOI":"10.1074\/jbc.M303248200","article-title":"Hepatitis C Virus NS5A and Subgenomic Replicon Activate NF-\u03baB via Tyrosine Phosphorylation of I\u03baB\u03b1 and Its Degradation by Calpain Protease","volume":"278","author":"G Waris","year":"2003","journal-title":"J Biol Chem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.2353\/ajpath.2007.070413","article-title":"Responses of Nontransformed Human Hepatocytes to Conditional Expression of Full-Length Hepatitis C Virus Open Reading Frame","volume":"171","author":"W Tang","year":"2007","journal-title":"Am J Pathol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1136\/gut.2005.070417","article-title":"Hepatitis C virus core protein promotes proliferation of human hepatoma cells through enhancement of transforming growth factor \u03b1 expression via activation of nuclear factor-\u03baB","volume":"55","author":"Y Sato","year":"2006","journal-title":"Gut"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1002\/hep.24763","article-title":"Activation of chemokine and inflammatory cytokine response in hepatitis C virus\u2013infected hepatocytes depends on toll-like receptor 3 sensing of hepatitis C virus double-stranded RNA intermediates","volume":"55","author":"K Li","year":"2012","journal-title":"Hepatology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1111\/j.1365-2893.2011.01505.x","article-title":"Inhibition of I\u03baB kinase by thalidomide increases hepatitis C virus RNA replication","volume":"19","author":"E Rance","year":"2012","journal-title":"J Viral Hepat"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.virol.2013.01.015","article-title":"The modulation of hepatitis C virus 1a replication by PKR is dependent on NF-kB mediated interferon beta response in Huh7.5.1 cells","volume":"438","author":"L Zhang","year":"2013","journal-title":"Virology"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1002\/hep.510310316","article-title":"Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis","volume":"31","author":"DI Tai","year":"2000","journal-title":"Hepatology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1365-2362.2010.02295.x","article-title":"NF\u03baB, cytokines, TLR 3 and 7 expression in human end-stage HCV and alcoholic liver disease","volume":"40","author":"P St\u00e4rkel","year":"2010","journal-title":"Eur J Clin Invest"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1111\/j.1462-5822.2012.01773.x","article-title":"Interaction networks of hepatitis C virus NS4B: implications for antiviral therapy","volume":"14","author":"S Li","year":"2012","journal-title":"Cell Microbiol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"5974","DOI":"10.1128\/JVI.76.12.5974-5984.2002","article-title":"Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex","volume":"76","author":"D Egger","year":"2002","journal-title":"J Virol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.virusres.2007.03.020","article-title":"Inhibition of HCV RNA-dependent RNA polymerase activity by aqueous extract from Fructus Ligustri Lucidi","volume":"128","author":"L Kong","year":"2007","journal-title":"Virus Res"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.antiviral.2013.02.003","article-title":"Oleanolic acid and ursolic acid: Novel hepatitis C virus antivirals that inhibit NS5B activity","volume":"98","author":"L Kong","year":"2013","journal-title":"Antiviral Res"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"12531","DOI":"10.1128\/JVI.01136-12","article-title":"Hepatitis C virus activates Bcl-2 and MMP-2 expression through multiple cellular signaling pathways","volume":"86","author":"Y Li","year":"2012","journal-title":"J Virol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"C1082","DOI":"10.1152\/ajpcell.00217.2006","article-title":"Mitochondrial reactive oxygen species and Ca2+ signaling","volume":"291","author":"C Camello-Almaraz","year":"2006","journal-title":"Am J Physiol Cell Physiol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virusres.2012.04.006","article-title":"HCV NS4B induces apoptosis through the mitochondrial death pathway","volume":"169","author":"P Zhao","year":"2012","journal-title":"Virus Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.antiviral.2012.07.006","article-title":"Therapeutic vaccination against chronic hepatitis C virus infection","volume":"96","author":"PP Ip","year":"2012","journal-title":"Antiviral Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1038\/embor.2009.243","article-title":"IKK\/NF\u2014\u03baB and STAT3 pathways: central signalling hubs in inflammation\u2010mediated tumour promotion and metastasis","volume":"10","author":"J Bollrath","year":"2009","journal-title":"EMBO Rep"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/mnfr.201300362","article-title":"Quercetin prevents liver carcinogenesis by inducing cell cycle arrest, decreasing cell proliferation and enhancing apoptosis","volume":"58","author":"ML Casella","year":"2013","journal-title":"Mol Nutr Food Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/jpi.12092","article-title":"Inhibition of matrix metalloproteinase-9 and nuclear factor kappa B contribute to melatonin prevention of motility and invasiveness in HepG2 liver cancer cells","volume":"56","author":"R Ordo\u00f1ez","year":"2014","journal-title":"J Pineal Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/carcin\/bgt335","article-title":"CYLD controls c-MYC expression through the JNK-dependent signaling pathway in hepatocellular carcinoma","volume":"35","author":"RR Pannem","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1089\/thy.2012.0237","article-title":"The nuclear factor kappa-B signaling pathway as a therapeutic target against thyroid cancers","volume":"23","author":"X Li","year":"2012","journal-title":"Thyroid"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.bbadis.2013.06.001","article-title":"Overexpression of c-myc in hepatocytes promotes activation of hepatic stellate cells and facilitates the onset of liver fibrosis","volume":"1832","author":"YA Nevzorova","year":"2013","journal-title":"Biochim biophys Acta"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jhep.2012.01.027","article-title":"Bak deficiency inhibits liver carcinogenesis: A causal link between apoptosis and carcinogenesis","volume":"57","author":"H Hikita","year":"2012","journal-title":"J Hepatol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1038\/onc.2012.318","article-title":"MicroRNA-125b promotes apoptosis by regulating the expression of Mcl-1, Bcl-w and IL-6R","volume":"32","author":"J Gong","year":"2013","journal-title":"Oncogene"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"9599","DOI":"10.1073\/pnas.171311298","article-title":"Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-\u03baB","volume":"98","author":"G Gong","year":"2001","journal-title":"Proc Natl Acas Sci U S A"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/hep.22108","article-title":"The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection","volume":"47","author":"S Einav","year":"2008","journal-title":"Hepatology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/jmv.20283","article-title":"Hepatitis C virus core, NS3, NS5A, NS5B proteins induce apoptosis in mature dendritic cells","volume":"75","author":"S Siavoshian","year":"2005","journal-title":"J Med Virol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1006\/viro.1996.8420","article-title":"Sensitization to Fas-mediated apoptosis by hepatitis C virus core protein","volume":"229","author":"A Ruggieri","year":"1997","journal-title":"Virology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"4713","DOI":"10.1128\/JVI.73.6.4713-4720.1999","article-title":"Hepatitis C virus core protein inhibits Fas- and tumor necrosis factor alpha-mediated apoptosis via NF-kappaB activation","volume":"73","author":"H Marusawa","year":"1999","journal-title":"J Virol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1055\/s-2007-991513","article-title":"Endoplasmic reticulum stress and liver injury","volume":"27","author":"N Kaplowitz","year":"2007","journal-title":"Semin Liver Dis"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1172\/JCI26373","article-title":"Endoplasmic reticulum stress: cell life and death decisions","volume":"115","author":"C Xu","year":"2005","journal-title":"J Clin Invest"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/1471-2407-14-98","article-title":"Regulation of Mcl-1 by constitutive activation of NF-kappaB contributes to cell viability in human esophageal squamous cell carcinoma cells","volume":"14","author":"H Liu","year":"2014","journal-title":"BMC Cancer"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1089\/aid.2011.0263","article-title":"Transcriptional control of HIV replication by multiple modulators and their implication for a novel antiviral therapy","volume":"28","author":"AF Victoriano","year":"2012","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1515\/BC.2008.148","article-title":"Influenza viruses and the NF-kappaB signaling pathway\u2014towards a novel concept of antiviral therapy","volume":"389","author":"S Ludwig","year":"2008","journal-title":"Biol Chem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1006\/scbi.1997.0063","article-title":"The role of Rel\/NF-\u03baB proteins in viral oncogenesis and the regulation of viral transcription","volume":"8","author":"G Mosialos","year":"1997","journal-title":"Semin Cancer Biol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0123190","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T22:53:59Z","timestamp":1598914439000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0123190"}},"subtitle":[],"editor":[{"given":"Naglaa H.","family":"Shoukry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,4,13]]},"references-count":45,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,4,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0123190","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,13]]}}}