title: The metabolic responses to hepatitis B virus infection shed new light on pathogenesis and targets for treatment.
abstract: 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.
authors: 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.
authors: Hongde
authors: H
authors: Li
authors: 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.
authors: Wandi
authors: W
authors: Zhu
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors: Leike
authors: L
authors: Zhang
authors: 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.
authors: Hehua
authors: H
authors: Lei
authors: 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.
authors: Xiangyu
authors: X
authors: Wu
authors: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors: Lin
authors: L
authors: Guo
authors: State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors: Xinwen
authors: X
authors: Chen
authors: 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] Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310058, China.
authors: Yulan
authors: Y
authors: Wang
authors: 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] State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Metabolomics and Systems Biology Laboratory, School of Life Sciences, Fudan University, Shanghai, 200433, P.R. China.
authors: Huiru
authors: H
authors: Tang
mesh_terms: D053898:Biosynthetic Pathways; D045744:Cell Line, Tumor; D002952:Citric Acid Cycle; D005110:Extracellular Space; D006509:Hepatitis B / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006595:Hexosamines / Q000096:biosynthesis; D006801:Humans; D042541:Intracellular Space; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D055432:Metabolomics; D018384:Oxidative Stress; D010713:Phosphatidylcholines / Q000096:biosynthesis; D014779:Virus Replication
chemical_list: D006595:Hexosamines; D010713:Phosphatidylcholines