Transcriptomic and proteomic study of HBsAg positive transgenic mouse liver suggests that viral protein affects the hepatocellular metabolism of sugar, lipid and amino acids
1.Key Laboratory of Medical Molecular Virology of Ministry of Education and Public Health of China, Shanghai Medical School, Fudan University, Shanghai 200032, China; 2.Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical School, Fudan University, Shanghai 200032, China
Abstract:Objective Utilize the transgenic mouse lineage # 59 which mimics human HBsAg positive carriers, to investigate mechanisms of cellular response involved in HBsAg persistence. Methods Affymertix DNA microarray was used to observe the differential gene expression of the transgenic mouse liver compared to the sibling controls which were HBsAg negative. Proteomic experiments were conducted to identify the alterations of enzymes involved in metabolism in e transgenic mouse liver. Results Microarray showed that 43 genes were significantly (≥2 folds) up regulated and 104 genes were significantly down regulated in the transgenic mouse liver. Eighteen enzymes associated with metabolisms were identified by proteomic studies with increased levels (≥1.5 folds) and 9 enzymes with decreased levels in the transgenic mouse liver. Conclusion The persistence of HBsAg markedly affected host liver cell metabolism. Specifically, cholesterol biosynthesis was increased while bile acid synthesis was diminished. While glycolysis activity was reduced, the gluconeogenesis activity was increased. Amino acid catabolism was increased and urea synthesis was decreased. The potential biological impact of these metabolic alterations in HBV persistent infection was discussed.
Transcriptomic and proteomic study of HBsAg positive transgenic mouse liver suggests that viral protein affects the hepatocellular metabolism of sugar, lipid and amino acids
. Journal of Microbes and Infections, 2006, 1(1): 7-14 .