Hepatitis B virus surface antigen interacts with acid alpha-glucosidase and alters glycogen metabolism

Jui Hsiang Hung, Chiao Wen Yan, Ih Jen Su, Hui Ching Wang, Huan Yao Lei, Wan Chi Lin, Wen Tsan Chang, Wenya Huang, Te Jung Lu, Ming Derg Lai

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Aim: 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-S2Δ) by using human liver cDNA library, and identified the acid alpha-glucosidase (acid α-glucosidase) as the novel cellular interacting protein of pre-S2Δ. The association of pre-S2Δ with the acid α-glucosidase was confirmed by confocal immunofluorescence and co-immunoprecipitation assay. Further, the acid α-glucosidase activity and glycogen content were analyzed in ML-1 cells expressing pre-S2Δ. Results: The interaction between HBV large surface protein and acid α-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 α-glucosidase. On the other hand, HBV large surface protein interacted with acid α-glucosidase through N-terminal region 1-157 amino acid of HBV large surface protein. Expression of HBV large surface protein enhanced acid α-glucosidase activity and resulted in decrease of cellular glycogen. Conclusion: Our result demonstrates that HBV large surface protein interacts with acid α-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.

Original languageEnglish
Pages (from-to)633-640
Number of pages8
JournalHepatology Research
Issue number6
Publication statusPublished - 2010 Jun

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Infectious Diseases


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