title: Hepatitis B virus surface antigen interacts with acid alpha-glucosidase and alters glycogen metabolism.
abstract: OBJECTIVE
  Hepatitis B virus (HBV) infection is highly correlated with hepatocellular carcinoma. Previous studies have reported that expression of hepatitis B virus pre-S2 mutant surface antigen is related to hepatoma development. An aberrant carbohydrate metabolism is a hallmark of malignant transformation.
  
  
  METHODS
  We performed yeast two-hybrid screening with HBV pre-S2-del large surface protein (pre-S2Delta) by using human liver cDNA library, and identified the acid alpha-glucosidase (acid alpha-glucosidase) as the novel cellular interacting protein of pre-S2Delta. The association of pre-S2Delta with the acid alpha-glucosidase was confirmed by confocal immunofluorescence and co-immunoprecipitation assay. Further, the acid alpha-glucosidase activity and glycogen content were analyzed in ML-1 cells expressing pre-S2Delta.
  
  
  RESULTS
  The interaction between HBV large surface protein and acid alpha-glucosidase was demonstrated with co-immunoprecipitation in vitro and in vivo, and the binding was mediated through c-terminal region 889-952 amino acid of acid alpha-glucosidase. On the other hand, HBV large surface protein interacted with acid alpha-glucosidase through N-terminal region 1-157 amino acid of HBV large surface protein. Expression of HBV large surface protein enhanced acid alpha-glucosidase activity and resulted in decrease of cellular glycogen.
  
  
  CONCLUSIONS
  Our result demonstrates that HBV large surface protein interacts with acid alpha-glucosidase which plays an important role in glycogen balance. Together, these data suggest a novel pathway by which HBV large surface protein affects carbohydrate metabolism.
authors.affiliation: Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Email: a1211207@mail.ncku.edu.tw.
authors.forename: Jui-Hsiang
authors.initials: JH
authors.lastname: Hung
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Yan
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Wang
authors.forename: Huan-Yao
authors.initials: HY
authors.lastname: Lei
authors.forename: Wan-Chi
authors.initials: WC
authors.lastname: Lin
authors.forename: Wen-Tsan
authors.initials: WT
authors.lastname: Chang
authors.forename: Wenya
authors.initials: W
authors.lastname: Huang
authors.forename: Te-Jung
authors.initials: TJ
authors.lastname: Lu
authors.forename: Ming-Derg
authors.initials: MD
authors.lastname: Lai