Hepatitis B virus surface antigen interacts with acid alpha-glucosidase and alters glycogen metabolism.
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.
Hung
Jui-Hsiang
JH
Department of Biochemistry, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Email: a1211207@mail.ncku.edu.tw.
Yan
Chiao-Wen
CW
Su
Ih-Jen
IJ
Wang
Hui-Ching
HC
Lei
Huan-Yao
HY
Lin
Wan-Chi
WC
Chang
Wen-Tsan
WT
Huang
Wenya
W
Lu
Te-Jung
TJ
Lai
Ming-Derg
MD