Li Hongde, Zhu Wandi, Zhang Leike, Lei Hehua, Wu Xiangyu, Guo Lin, Chen Xinwen, Wang Yulan, Tang Huiru
1] Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
1] State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China [2] University of Chinese Academy of Sciences, Beijing 100049, China.
Sci Rep. 2015 Feb 12;5:8421. doi: 10.1038/srep08421.
Chronic infection caused by the hepatitis B virus (HBV), is strongly associated with hepatitis, fatty liver and hepatocellular carcinoma. To investigate the underlying mechanisms, we characterize the metabolic features of host cells infected with the virus using systems biological approach. The results show that HBV replication induces systematic metabolic alterations in host cells. HBV infection up-regulates the biosynthesis of hexosamine and phosphatidylcholine by activating glutamine-fructose-6-phosphate amidotransferase 1 (GFAT1) and choline kinase alpha (CHKA) respectively, which were reported for the first time for HBV infection. Importantly suppressing hexosamine biosynthesis and phosphatidylcholine biosynthesis can inhibit HBV replication and expression. In addition, HBV induces oxidative stress and stimulates central carbon metabolism and nucleotide synthesis. Our results also indicate that HBV associated hepatocellular carcinoma could be attributed to GFAT1 activated hexosamine biosynthesis and CHKA activated phosphatidylcholine biosynthesis. This study provides further insights into the pathogenesis of HBV-induced diseases, and sheds new light on drug target for treating HBV infection.
乙型肝炎病毒（HBV）引起的慢性感染与肝炎、脂肪肝和肝细胞癌密切相关。为了探究其潜在机制，我们采用系统生物学方法对感染该病毒的宿主细胞的代谢特征进行了表征。结果表明，HBV复制会诱导宿主细胞发生系统性代谢改变。HBV感染分别通过激活谷氨酰胺-果糖-6-磷酸酰胺转移酶1（GFAT1）和胆碱激酶α（CHKA）来上调己糖胺和磷脂酰胆碱的生物合成，这是首次报道HBV感染会出现这种情况。重要的是，抑制己糖胺生物合成和磷脂酰胆碱生物合成可以抑制HBV复制和表达。此外，HBV会诱导氧化应激并刺激中心碳代谢和核苷酸合成。我们的研究结果还表明，与HBV相关的肝细胞癌可能归因于GFAT1激活的己糖胺生物合成和CHKA激活的磷脂酰胆碱生物合成。本研究为HBV诱导疾病的发病机制提供了进一步的见解，并为治疗HBV感染的药物靶点提供了新的思路。
