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

  • RESEARCH ARTICLE
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Virologica Sinica

A Correction to this article was published on 24 November 2021

This article has been updated

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.

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Acknowledgements

This research was funded by the National Major Science and Technology Projects of China, grant number 2017ZX10202203-007-003.

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Author notes

  1. Mengyuan Li and Jiali Yang have contributed equally to this work.

Authors and Affiliations

  1. Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University, **’an, 710038, China

    Mengyuan Li, Chuantao Ye, Peiyu Bian, **aofei Yang & Jianqi Lian

  2. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, **’an, 710069, China

    Jiali Yang

  3. Department of Neurology, ****g Hospital, Air Force Medical University, **’an, 710032, China

    Haijun Zhang

  4. Pathogenic Biology, Medical College of Yan’an University, Yan’an, 716000, China

    Chuanyu Luo & Zhifeng Xue

  5. Department of Microbiology, School of Preclinical Medicine, Air Force Medical University, **’an, 710032, China

    Yingfeng Lei

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  1. Mengyuan Li
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Contributions

JL and YL designed the experiments. ML and JY carried out the experiments and wrote the original draft. CY, XY, HZ, CL and ZX analyzed the data. JL and YL reviewed the manuscript and provided the financial support. All authors read and approved the final manuscript.

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Correspondence to Yingfeng Lei or Jianqi Lian.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Li, M., Yang, J., Ye, C. et al. Integrated Metabolomics and Transcriptomics Analyses Reveal Metabolic Landscape in Neuronal Cells during JEV Infection. Virol. Sin. 36, 1554–1565 (2021). https://doi.org/10.1007/s12250-021-00445-0

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