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Title 

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

Authors 

A G WangD S LeeH B MoonJ M KimK H ChoS H ChoiH L HaY H HanD G KimS B HwangDae Yeul Yu

Publisher 

Wiley-Blackwell

Issue Date 

2009

Citation 

Journal of Pathology, vol. 219, no. 2, pp. 253-262

Keywords 

Hepatitis C virusLiver pathogenesisNS5A proteinSteatosisTransgenic mice

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.

ISSN 

0022-3417

Link 

http://dx.doi.org/10.1002/path.2592

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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