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However, the mechanism of HCV pathogenesis is not well understood. Our previous\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies suggested that non\u2010structural 5A (NS5A) protein may play an important role in liver pathogenesis. To elucidate the mechanism of HCV\u2010induced liver pathogenesis, we investigated the histopathological changes of liver in transgenic mice harbouring the\n                    <jats:italic>NS5A<\/jats:italic>\n                    gene. We generated transgenic mice harbouring HCV\n                    <jats:italic>NS5A<\/jats:italic>\n                    gene under the control of hepatitis B virus (HBV) enhancer. Pathological changes were analysed by immunohistochemical staining and western blot analysis. Lipid composition and reactive oxygen species (ROS) production in NS5A transgenic mice were analysed. HCV NS5A transgenic mice developed extraordinary steatosis over 6 months old and induced HCC in some mice. NS5A was co\u2010localized with apolipoprotein A\u2010I in fatty hepatocytes. In addition, the extraordinarily high levels of ROS, NF\u2010\u03baB and STAT3 were detected in hepatocytes of NS5A transgenic mice. These data suggest that NS5A, independent of other HCV viral proteins, may play an important role in the development of hepatic pathologies, including steatosis and hepatoceullular carcinoma in transgenic mice. Copyright \u00a9 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2592","type":"journal-article","created":{"date-parts":[[2009,6,18]],"date-time":"2009-06-18T05:13:05Z","timestamp":1245301985000},"page":"253-262","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Non\u2010structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic 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