School of Basic Medical Sciences, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery of Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
State Key Laboratory of Proteomics, Beijing Proteome Research Centre, National Engineering Research Centre for Protein Drugs, National Centre for Protein Sciences Beijing, Institute of Radiation Medicine, Beijing 102206, China.
Sci Rep. 2017 Jan 23;7:41089. doi: 10.1038/srep41089.
Chronic hepatitis B virus (HBV) infection is partly responsible for hepatitis, fatty liver disease and hepatocellular carcinoma (HCC). HBV core protein (HBc), encoded by the HBV genome, may play a significant role in HBV life cycle. However, the function of HBc in the occurrence and development of liver disease is still unclear. To investigate the underlying mechanisms, HBc-transfected HCC cells were characterized by multi-omics analyses. Combining proteomics and metabolomics analyses, our results showed that HBc promoted the expression of metabolic enzymes and the secretion of metabolites in HCC cells. In addition, glycolysis and amino acid metabolism were significantly up-regulated by HBc. Moreover, Max-like protein X (MLX) might be recruited and enriched by HBc in the nucleus to regulate glycolysis pathways. This study provides further insights into the function of HBc in the molecular pathogenesis of HBV-induced diseases and indicates that metabolic reprogramming appears to be a hallmark of HBc transfection.
慢性乙型肝炎病毒（HBV）感染是导致肝炎、脂肪肝和肝细胞癌（HCC）的部分原因。HBV 基因组编码的核心蛋白（HBc）可能在 HBV 生命周期中发挥重要作用。然而，HBc 在肝病发生和发展中的功能尚不清楚。为了研究潜在机制，我们对 HBc 转染的 HCC 细胞进行了多组学分析。通过蛋白质组学和代谢组学分析，我们的结果表明 HBc 促进了 HCC 细胞中代谢酶的表达和代谢物的分泌。此外，HBc 显著上调了糖酵解和氨基酸代谢。此外，Max-like 蛋白 X（MLX）可能被 HBc 募集并富集到细胞核中，以调节糖酵解途径。本研究进一步深入了解了 HBc 在 HBV 诱导疾病的分子发病机制中的作用，并表明代谢重编程似乎是 HBc 转染的标志。
