{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:43:41Z","timestamp":1790613821672,"version":"4.1.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T00:00:00Z","timestamp":1503964800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,29]],"date-time":"2017-08-29T00:00:00Z","timestamp":1503964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. To address the molecular basis of HCV pathogenesis using tupaias (<jats:italic>Tupaia belangeri<\/jats:italic>), we characterized host responses upon HCV infection. Adult tupaias were infected with HCV genotypes 1a, 1b, 2a, or 4a. Viral RNA, alanine aminotransferase, anti-HCV core and anti-nonstructural protein NS3 antibody titres, reactive oxygen species (ROS), and anti-3\u03b2-hydroxysterol-\u039424reductase (DHCR24) antibody levels were measured at 2-week intervals from 0 to 41 weeks postinfection. All HCV genotypes established infections and showed intermittent HCV propagation. Moreover, all tupaias produced anti-core and anti-NS3 antibodies. ROS levels in sera and livers were significantly increased, resulting in induction of DHCR24 antibody production. Similarly, lymphocytic infiltration, disturbance of hepatic cords, and initiation of fibrosis were observed in livers from HCV-infected tupaias. Intrahepatic levels of Toll-like receptors 3, 7, and 8 were significantly increased in all HCV-infected tupaias. However, interferon-\u03b2 was only significantly upregulated in HCV1a- and HCV2a-infected tupaias, accompanied by downregulation of sodium taurocholate cotransporting polypeptide. Thus, our findings showed that humoral and innate immune responses to HCV infection, ROS induction, and subsequent increases in DHCR24 auto-antibody production occurred in our tupaia model, providing novel insights into understanding HCV pathogenesis.<\/jats:p>","DOI":"10.1038\/s41598-017-10329-7","type":"journal-article","created":{"date-parts":[[2017,8,23]],"date-time":"2017-08-23T13:18:43Z","timestamp":1503494323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Oxidative Stress and Immune Responses During Hepatitis C Virus Infection in Tupaia belangeri"],"prefix":"10.1038","volume":"7","author":[{"given":"Mohammad Enamul Hoque","family":"Kayesh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayeh","family":"Ezzikouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Sanada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija","family":"Rebbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bouchra","family":"Kitab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Matsuu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunekazu","family":"Hishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michinori","family":"Kohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Tsukiyama-Kohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,29]]},"reference":[{"issue":"Suppl 1","key":"10329_CR1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/j.1478-3231.2008.01934.x","volume":"29","author":"D Lavanchy","year":"2009","unstructured":"Lavanchy, D. The global burden of hepatitis C. Liver international: official journal of the International Association for the Study of the Liver \n                           29(Suppl 1), 74\u201381 (2009).","journal-title":"Liver international: official journal of the International Association for the Study of the Liver"},{"key":"10329_CR2","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1002\/hep.26141","volume":"57","author":"K Mohd Hanafiah","year":"2013","unstructured":"Mohd Hanafiah, K., Groeger, J., Flaxman, A. D. & Wiersma, S. T. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology \n                           57, 1333\u20131342 (2013).","journal-title":"Hepatology"},{"key":"10329_CR3","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1038\/nm.3253","volume":"19","author":"SM Horner","year":"2013","unstructured":"Horner, S. M. & Gale, M. 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