Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice

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Title
Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice
Author(s)
A G Wang; D S Lee; H B Moon; J M Kim; K H Cho; S H Choi; H L Ha; Y H Han; D G Kim; S B Hwang; Dae Yeul Yu
Bibliographic Citation
Journal of Pathology, vol. 219, no. 2, pp. 253-262
Publication Year
2009
Abstract
Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). However, the mechanism of HCV pathogenesis is not well understood. Our previous in vitro studies suggested that non-structural 5A (NS5A) protein may play an important role in liver pathogenesis. To elucidate the mechanism of HCV-induced liver pathogenesis, we investigated the histopathological changes of liver in transgenic mice harbouring the NS5A gene. We generated transgenic mice harbouring HCV NS5A 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-localized with apolipoprotein A-I in fatty hepatocytes. In addition, the extraordinarily high levels of ROS, NF-κB 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.
Keyword
Hepatitis C virusLiver pathogenesisNS5A proteinSteatosisTransgenic mice
ISSN
0022-3417
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/path.2592
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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