{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:02:02Z","timestamp":1761217322237,"version":"3.38.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1949,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Fibrinogen-\u03b2 (FBG-\u03b2), an important acute-phase protein (APP), is generated by the liver as a target for inflammatory mediators. Here we identified FBG-\u03b2 as a hepatitis C virus (HCV) core interacting protein by screening a human liver complementary DNA (cDNA) library using mammalian two-hybrid analysis. An association between FBG-\u03b2 and HCV core protein was verified by confocal microscopy and coimmunoprecipitation from the transfected human hepatocyte (Huh-7) cell line. HCV core or genomic RNA transfected Huh-7 cells modestly increased FBG-\u03b2 protein expression when compared to the basal level in control hepatocytes. Transfection of HCV core or full-length (FL) gene into Huh-7 cells up-regulated basal FBG-\u03b2 promoter activity. Exogenous addition of IL-6 stimulates FBG-\u03b2 promoter activity in hepatocytes. However, ectopic expression of HCV core or FL in hepatocytes inhibited IL-6-stimulated FBG-\u03b2 promoter activation. Inhibition of endogenous FBG-\u03b2 expression following introduction of small interfering RNA (siRNA) into cells displayed a gain of function of promoter regulation by HCV core protein. Further studies suggested that HCV core gene expression in stable transfectants of Huh-7 cells resulted in a basal up-regulation of FBG-\u03b2 and other APPs. However, treatment with cytokines, interleukin-6 (IL-6), or tumor necrosis factor-\u03b1 repressed FBG-\u03b2 and other acute-phase response (APR) genes.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>Our results reveal that the core\/FBG-\u03b2 interaction may act as a regulatory feedback, allowing repression of IL-6-stimulated APR genes. Together, these data suggested a network of interactions between HCV core and the hepatic APR genes, and may contribute to impaired innate immunity for viral persistence. (Hepatology 2010.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.23502","type":"journal-article","created":{"date-parts":[[2009,12,10]],"date-time":"2009-12-10T19:10:39Z","timestamp":1260472239000},"page":"1505-1513","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":18,"title":["Hepatitis C Virus Core Protein Interacts With Fibrinogen-\u03b2 and Attenuates Cytokine Stimulated Acute-Phase Response"],"prefix":"10.1097","volume":"51","author":[{"given":"Malika","family":"Ait-Goughoulte","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arup","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Budhaditya","family":"Mazumdar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kousuke","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ratna B.","family":"Ray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranjit","family":"Ray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-7-20250312","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1056\/NEJM199902113400607","article-title":"Acutephase proteins and other systemic responses to inflammation.","volume":"340","author":"Gabay","year":"1999","journal-title":"N Engl J Med"},{"key":"R2-7-20250312","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1056\/NEJM200103223441207","article-title":"Cytokine pathways and joint inflammation in rheumatoid arthritis.","volume":"344","author":"Choy","year":"2001","journal-title":"N Engl J Med"},{"key":"R3-7-20250312","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/0167-5699(94)90137-6","article-title":"The acute phase response.","volume":"15","author":"Baumann","year":"1994","journal-title":"Immunol Today"},{"key":"R4-7-20250312","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0889-1591(03)00048-5","article-title":"The inflammatory response is an integral part of the stress response: implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X.","volume":"17","author":"Black","year":"2003","journal-title":"Brain Behav Immun"},{"key":"R5-7-20250312","doi-asserted-by":"crossref","first-page":"7251","DOI":"10.1073\/pnas.84.20.7251","article-title":"Interferon beta 2Bcell stimulatory factor type 2 shares identity with monocytederived hepatocytestimulating factor and regulates the major acute phase protein response in liver cells.","volume":"84","author":"Gauldie","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R6-7-20250312","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0014-5793(89)80476-4","article-title":"Interleukin6 is the major regulator of acute phase protein synthesis in adult human hepatocytes.","volume":"242","author":"Castell","year":"1989","journal-title":"FEBS Lett"},{"key":"R7-7-20250312","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1083\/jcb.105.3.1067","article-title":"The coordinated regulation of fibrinogen gene transcription by hepatocytestimulating factor and dexamethasone.","volume":"105","author":"Otto","year":"1987","journal-title":"J Cell Biol"},{"key":"R8-7-20250312","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1182\/blood.V89.3.873","article-title":"Induction of fibrinogen biosynthesis and secretion from cultured pulmonary epithelial cells.","volume":"89","author":"SimpsonHaidaris","year":"1997","journal-title":"Blood"},{"key":"R9-7-20250312","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1182\/blood.V96.10.3466","article-title":"Interleukin1 inhibits interleukin 6mediated rat fibrinogen gene expression.","volume":"96","author":"Zhang","year":"2000","journal-title":"Blood"},{"key":"R10-7-20250312","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1136\/ard.2005.043232","article-title":"Differential influence of p38 mitogen activated protein kinase (MAPK) inhibition on acute phase protein synthesis in human hepatoma cell lines.","volume":"65","author":"Westra","year":"2006","journal-title":"Ann Rheum Dis"},{"key":"R11-7-20250312","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.4049\/jimmunol.167.3.1469","article-title":"The inhibitory effect of IL1 on IL6induced 2macroglobulin expression is due to activation of NFB.","volume":"167","author":"Bode","year":"2001","journal-title":"J Immunol"},{"key":"R12-7-20250312","doi-asserted-by":"crossref","first-page":"30607","DOI":"10.1074\/jbc.272.49.30607","article-title":"STAT3 acts as a coactivator of glucocorticoid receptor signaling.","volume":"272","author":"Zhang","year":"1997","journal-title":"J Biol Chem"},{"key":"R13-7-20250312","doi-asserted-by":"crossref","first-page":"9722972","DOI":"10.1128\/JVI.72.12.9722-9728.1998","article-title":"Ectopic expression of hepatitis C virus core protein differentially regulates nuclear transcription factors.","volume":"72","author":"Shrivastava","year":"1998","journal-title":"J Virol"},{"key":"R14-7-20250312","first-page":"347","article-title":"Microarray analyses and molecular profiling of Stat3 signaling pathway induced by hepatitis C virus core protein in human hepatocytes.","volume":"49","author":"Basu","year":"2009","journal-title":"Virology"},{"key":"R15-7-20250312","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1002\/hep.510300318","article-title":"Modulation of hepatic acute phase gene expression by epidermal growth factor and src protein tyrosine kinases in murine and human hepatic cells.","volume":"30","author":"Wang","year":"1999","journal-title":"HEPATOLOGY"},{"key":"R16-7-20250312","doi-asserted-by":"crossref","first-page":"28562","DOI":"10.1074\/jbc.M210485200","article-title":"Hepatitis C virus core protein differently regulates the JAKSTAT signaling pathway under interleukin6 and interferongamma stimuli.","volume":"278","author":"Hosui","year":"2003","journal-title":"J Biol Chem"},{"key":"R17-7-20250312","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ymeth.2003.10.011","article-title":"A cDNA library functional screening strategy based on fluorescent protein complementation assays to identify novel components of signaling pathways.","volume":"32","author":"Remy","year":"2004","journal-title":"Methods (Duluth)"},{"key":"R18-7-20250312","first-page":"411","article-title":"Mapping biochemical networks with proteinfragment complementation assays.","volume":"261","author":"Remy","year":"2004","journal-title":"Methods Mol Biol"},{"key":"R19-7-20250312","doi-asserted-by":"crossref","first-page":"9663","DOI":"10.1128\/JVI.00872-09","article-title":"Hepatitis C virus core protein and cellular protein HAX1 promotes 5fluorouracil mediated hepatocyte growth inhibition.","volume":"83","author":"Banerjee","year":"2009","journal-title":"J Virol"},{"key":"R20-7-20250312","doi-asserted-by":"crossref","first-page":"16763","DOI":"10.1074\/jbc.M501973200","article-title":"A hepatocyte nuclear factor3 site in the fibrinogen promoter is important for interleukin 6induced expression, and its activity is influenced by the adjacent148CT polymorphism.","volume":"280","author":"Verschuur","year":"2005","journal-title":"J Biol Chem"},{"key":"R21-7-20250312","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1128\/JVI.75.3.1401-1407.2001","article-title":"Hepatitis C virus NS5A physically associates with p53 and regulates p21waf1 gene expression in a p53dependent manner.","volume":"75","author":"Majumder","year":"2001","journal-title":"J Virol"},{"key":"R22-7-20250312","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S0925-4439(96)00048-8","article-title":"Initiation of acute phase response and synthesis of cytokines.","volume":"1317","author":"Koj","year":"1996","journal-title":"Biochim Biophys Acta"},{"key":"R23-7-20250312","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1096\/fj.09-131458","article-title":"Capturing hostpathogen interactions by protein microarrays: identification of novel streptococcal proteins binding to human fibronectin, fibrinogen, and C4BP.","volume":"23","author":"Margarit","year":"2009","journal-title":"FASEB J"},{"key":"R24-7-20250312","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1365-2958.2005.04527.x","article-title":"2005. Human fibrinogen bound to Streptococcus pyogenes M protein inhibits complement deposition via the classical pathway.","volume":"56","author":"Carlsson","year":"2005","journal-title":"Mol Microbiol"},{"key":"R25-7-20250312","doi-asserted-by":"crossref","first-page":"50710","DOI":"10.1074\/jbc.M408570200","article-title":"Identification and characterization of the C3 binding domain of the Staphylococcus aureus extracellular fibrinogenbinding protein (Efb).","volume":"279","author":"Lee","year":"2004","journal-title":"J Biol Chem"},{"key":"R26-7-20250312","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0190-9622(96)80115-0","article-title":"Chronic hepatitis C, cryoglobulinemia, and cutaneous necrotizing vasculitis. Clinical, pathologic, and immunopathologic study of twelve patients.","volume":"34","author":"Daoud","year":"1996","journal-title":"J Am Acad Dermatol"},{"key":"R27-7-20250312","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1046\/j.1365-2249.2002.01729.x","article-title":"Complement C4 monitoring in the followup of chronic hepatitis C treatment.","volume":"127","author":"DumestrePerard","year":"2002","journal-title":"Clin Exp Immunol"},{"key":"R28-7-20250312","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1590\/S0100-879X2005000500017","article-title":"Effect of hepatitis C serology on Creactive protein in a cohort of Brazilian hemodialysis patients.","volume":"38","author":"Nascimento","year":"2005","journal-title":"Braz J Med Biol Res"},{"key":"R29-7-20250312","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1161\/01.CIR.103.18.2283","article-title":"Highdensity lipoprotein loses its antiinflammatory properties during acute influenza A infection.","volume":"103","author":"Van Lenten","year":"2001","journal-title":"Circulation"},{"key":"R30-7-20250312","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-2893.2005.00655.x","article-title":"Serum lipid pattern in chronic hepatitis C: histological and virological correlations.","volume":"13","author":"Siagris","year":"2006","journal-title":"J Viral Hepat"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.23502","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201005000-00007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T11:13:15Z","timestamp":1741777995000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201005000-00007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2010]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.23502","relation":{},"ISSN":["0270-9139"],"issn-type":[{"type":"print","value":"0270-9139"}],"subject":[],"published":{"date-parts":[[2010,5]]}}}