title: Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic 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-kappaB 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.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Wang
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.forename: Hyung-Bae
authors.initials: HB
authors.lastname: Moon
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
authors.forename: Soo-Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Hye-Lin
authors.initials: HL
authors.lastname: Ha
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Han
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
authors.forename: Soon B
authors.initials: SB
authors.lastname: Hwang
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D018450:Disease Progression; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005260:Female; D016174:Hepacivirus / Q000472:pathogenicity*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D014774:Virulence; D012324:RNA-Dependent RNA Polymerase
chemical_list: D016632:Apolipoprotein A-I; D005227:Fatty Acids; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase