{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:18:19Z","timestamp":1789975099092,"version":"4.0.1"},"reference-count":65,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T00:00:00Z","timestamp":1550016000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian INAIL-BRIC","award":["ID50 2016"],"award-info":[{"award-number":["ID50 2016"]}]},{"name":"Italian INAIL-BRIC","award":["N.18526 2016"],"award-info":[{"award-number":["N.18526 2016"]}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["ID50 2016"],"award-info":[{"award-number":["ID50 2016"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["N.18526 2016"],"award-info":[{"award-number":["N.18526 2016"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004008","name":"Istituto Superiore di Sanit\u00e0","doi-asserted-by":"publisher","award":["ID50 2016"],"award-info":[{"award-number":["ID50 2016"]}],"id":[{"id":"10.13039\/501100004008","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004008","name":"Istituto Superiore di Sanit\u00e0","doi-asserted-by":"publisher","award":["N.18526 2016"],"award-info":[{"award-number":["N.18526 2016"]}],"id":[{"id":"10.13039\/501100004008","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Arcobaleno Onlus","award":["ID50 2016"],"award-info":[{"award-number":["ID50 2016"]}]},{"name":"Arcobaleno Onlus","award":["N.18526 2016"],"award-info":[{"award-number":["N.18526 2016"]}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["ID50 2016"],"award-info":[{"award-number":["ID50 2016"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["N.18526 2016"],"award-info":[{"award-number":["N.18526 2016"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2019,2,13]]},"abstract":"<jats:p>Hepatitis C virus (HCV) is a blood-borne pathogen causing acute and chronic hepatitis. A significant number of people chronically infected with HCV develop cirrhosis and\/or liver cancer. The pathophysiologic mechanisms of hepatocyte damage associated with chronic HCV infection are not fully understood yet, mainly due to the lack of an <jats:italic>in vitro<\/jats:italic> system able to recapitulate the stages of infection <jats:italic>in vivo<\/jats:italic>. Several studies underline that HCV virus replication depends on redox-sensitive cellular pathways; in addition, it is known that virus itself induces alterations of the cellular redox state. However, the exact interplay between HCV replication and oxidative stress has not been elucidated. In particular, the role of reduced glutathione (GSH) in HCV replication and infection is still not clear. We set up an <jats:italic>in vitro<\/jats:italic> system, based on low m.o.i. of Huh7.5 cell line with a HCV infectious clone (J6\/JFH1), that reproduced the acute and persistent phases of HCV infection up to 76 days of culture. We demonstrated that the acute phase of HCV infection is characterized by the elevated levels of reactive oxygen species (ROS) associated in part with an increase of NADPH-oxidase transcripts and activity and a depletion of GSH accompanied by high rates of viral replication and apoptotic cell death. Conversely, the chronic phase is characterized by a reestablishment of reduced environment due to a decreased ROS production and increased GSH content in infected cells that might concur to the establishment of viral persistence. Treatment with the prooxidant auranofin of the persistently infected cultures induced the increase of viral RNA titer, suggesting that a prooxidant state could favor the reactivation of HCV viral replication that in turn caused cell damage and death. Our results suggest that targeting the redox-sensitive host-cells pathways essential for viral replication and\/or persistence may represent a promising option for contrasting HCV infection.<\/jats:p>","DOI":"10.1155\/2019\/6452390","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T18:38:24Z","timestamp":1550083104000},"page":"1-14","source":"Crossref","is-referenced-by-count":9,"title":["Counteraction of HCV-Induced Oxidative Stress Concurs to Establish Chronic Infection in Liver Cell Cultures"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3238-3280","authenticated-orcid":true,"given":"Simona","family":"Anticoli","sequence":"first","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0, Center for Gender-Specific Medicine, Rome, Italy"},{"name":"Department of Public Health and Infectious Diseases, Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Sapienza University of Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Amatore","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Sapienza University of Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Matarrese","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0, Center for Gender-Specific Medicine, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Sapienza University of Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8330-4381","authenticated-orcid":true,"given":"Anna Teresa","family":"Palamara","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Sapienza University of Rome, Italy"},{"name":"IRCSS San Raffaele Pisana, Department of Human Sciences and Promotion of the Quality of the Life, San Raffaele Open University, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4427-4823","authenticated-orcid":true,"given":"Lucia","family":"Nencioni","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Istituto Pasteur Italia-Fondazione Cenci-Bolognetti, Sapienza University of Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2987-3844","authenticated-orcid":true,"given":"Anna","family":"Ruggieri","sequence":"additional","affiliation":[{"name":"Istituto Superiore di Sanit\u00e0, Center for Gender-Specific Medicine, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.012"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.3390\/v1020126"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1007\/s00795-006-0313-z"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161226225"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100698200"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.171311298"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.2174\/1568009616666160926124043"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.30983"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.3.1569-1580.2005"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2009.06128.x"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02529-09"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9012580"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13904"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.3390\/v7062745"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/8341937"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024957"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2625"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23671"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20388"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307904"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872-034X.2007.00261.x"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000719"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1002\/biof.5520170101"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.014340-0"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.186684"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023641"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastrohep.2012.03.004"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.5812\/hepatmon.22069"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.06.021"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.24.13001-13014.2002"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1126\/science.1114016"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a118408"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.04.020"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14034705"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01059-09"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.52.070183.003431"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.45.070176.003015"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.3390\/molecules200712732"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328347bd77"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.153686"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2005.02.004"},{"issue":"11","key":"43","first-page":"4365","volume":"61","year":"2001","journal-title":"Cancer Research"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01307-06"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2005"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1007\/112_2018_10"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00017"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12343"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001271"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01747"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1007\/s40139-013-0024-9"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.04.019"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00321-06"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.01.127"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.07.001"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2695"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.07.008"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.2174\/138161211798357728"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.10.037"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.1086\/528377"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122772"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094460"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v7.i29.2880"},{"key":"64","doi-asserted-by":"publisher","DOI":"10.1097\/01.meg.0000231746.76136.4a"},{"key":"65","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.07.002"},{"key":"66","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0753-x"}],"updated-by":[{"DOI":"10.1155\/2019\/3712969","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T00:00:00Z","timestamp":1555545600000}}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2019\/6452390.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2019\/6452390.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2019\/6452390.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T18:38:30Z","timestamp":1550083110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/omcl\/2019\/6452390\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,13]]},"references-count":65,"alternative-id":["6452390","6452390"],"URL":"https:\/\/doi.org\/10.1155\/2019\/6452390","relation":{"erratum":[{"id-type":"doi","id":"10.1155\/2019\/3712969","asserted-by":"object"}]},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,13]]}}}