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Citation: Mengyuan Li, Jiali Yang, Chuantao Ye, Peiyu Bian, Xiaofei Yang, Haijun Zhang, Chuanyu Luo, Zhifeng Xue, Yingfeng Lei, Jianqi Lian. Integrated Metabolomics and Transcriptomics Analyses Reveal Metabolic Landscape in Neuronal Cells during JEV Infection [J].VIROLOGICA SINICA, 2021, 36(6) : 1554-1565.  http://dx.doi.org/10.1007/s12250-021-00445-0

Integrated Metabolomics and Transcriptomics Analyses Reveal Metabolic Landscape in Neuronal Cells during JEV Infection

  • Corresponding author: Yingfeng Lei, yflei@fmmu.edu.cn, ORCID: 0000-0002-1482-6124
    Jianqi Lian, lianjq@fmmu.edu.cn, ORCID: 0000-0002-5549-7590
  • Received Date: 25 April 2021
    Accepted Date: 09 August 2021
    Published Date: 24 September 2021
    Available online: 01 December 2021
  • Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis in endemic regions of Asia. The neurotropism of JEV and its high-efficiency replication in neurons are the key events for pathogenesis. Revealing the interplay between virus and host cells in metabolic facet is of great importance both for unraveling the pathogenesis mechanisms and providing novel antiviral targets. This study took advantage of the integration analysis of metabolomics and transcriptomics to depict the metabolic profiles of neurons during the early stage of JEV infection. Increased glycolysis and its branched pentose phosphate pathway (PPP) flux and impaired oxidative phosphorylation (OXPHOS) in glucose utilization, and the catabolic patterns of lipid metabolism were created to facilitate the biosynthesis of precursors needed for JEV replication in neurons. Pharmacological inhibitions of both glycolysis pathway and PPP in neurons suggested its indispensable role in maintaining the optimal propagation of JEV. In addition, analysis of metabolomic-transcriptomic regulatory network showed the pivotal biological function of lipid metabolism during JEV infection. Several pro-inflammatory lipid metabolites were significantly up-regulated and might partially be responsible for the progression of encephalitis. These unique metabolic reprogramming features might give deeper insight into JEV infected neurons and provide promising antiviral approaches targeting metabolism.


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    Integrated Metabolomics and Transcriptomics Analyses Reveal Metabolic Landscape in Neuronal Cells during JEV Infection

      Corresponding author: Yingfeng Lei, yflei@fmmu.edu.cn
      Corresponding author: Jianqi Lian, lianjq@fmmu.edu.cn
    • 1. Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University, Xioan 710038, China
    • 2. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xioan 710069, China
    • 3. Department of Neurology, Xijing Hospital, Air Force Medical University, Xioan 710032, China
    • 4. Pathogenic Biology, Medical College of Yanoan University, Yanoan 716000, China
    • 5. Department of Microbiology, School of Preclinical Medicine, Air Force Medical University, Xioan 710032, China

    Abstract: 

    Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis in endemic regions of Asia. The neurotropism of JEV and its high-efficiency replication in neurons are the key events for pathogenesis. Revealing the interplay between virus and host cells in metabolic facet is of great importance both for unraveling the pathogenesis mechanisms and providing novel antiviral targets. This study took advantage of the integration analysis of metabolomics and transcriptomics to depict the metabolic profiles of neurons during the early stage of JEV infection. Increased glycolysis and its branched pentose phosphate pathway (PPP) flux and impaired oxidative phosphorylation (OXPHOS) in glucose utilization, and the catabolic patterns of lipid metabolism were created to facilitate the biosynthesis of precursors needed for JEV replication in neurons. Pharmacological inhibitions of both glycolysis pathway and PPP in neurons suggested its indispensable role in maintaining the optimal propagation of JEV. In addition, analysis of metabolomic-transcriptomic regulatory network showed the pivotal biological function of lipid metabolism during JEV infection. Several pro-inflammatory lipid metabolites were significantly up-regulated and might partially be responsible for the progression of encephalitis. These unique metabolic reprogramming features might give deeper insight into JEV infected neurons and provide promising antiviral approaches targeting metabolism.