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A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
Hepatitis B virus surface antigen interacts with acid alpha-glucosidase and alters glycogen metabolism
Jui-Hsiang Hung1, Chiao-Wen Yan, Ih-Jen Su
1Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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-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.
Conclusion:
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.
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