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Axl Alleviates Neuroinflammation and Delays Japanese Encephalitis Progression in Mice

  • RESEARCH ARTICLE
  • Published:
Virologica Sinica

Abstract

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus, which causes the most commonly diagnosed viral encephalitis named Japanese encephalitis (JE) in the world with an unclear pathogenesis. Axl, a receptor tyrosine kinase from TAM family, plays crucial role in many inflammatory diseases. We have previously discovered that Axl deficiency resulted in more severe body weight loss in mice during JEV infection, which we speculate is due to the anti-inflammatory effect of Axl during JE. Currently, the role of Axl in regulating the neuroinflammation and brain damage during JE has not been investigated yet. In this study, by using Axl deficient and heterozygous control mice, we discovered that Axl deficient mice displayed accelerated JE progression and exacerbated brain damage characterized by increased neural cell death, extended infiltration of inflammatory cells, and enhanced production of pro-inflammatory cytokines, in comparison to control mice. Additionally, consistent with our previous report, Axl deficiency had no impact on the infection and target cell tropism of JEV in brain. Taken together, our results suggest that Axl plays an anti-inflammatory and neuroprotective role during the pathogenesis of JE.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81671971, 81871641, 81972979, U1902210 and U1602223), the Scientific Research Plan of the Beijing Municipal Education Committee (KM201710025002), and the Key Project of Beijing Natural Science Foundation B (KZ201810025035), the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan (IDHT20190510).

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Author notes

  1. Zhao-Yang Wang and Zi-Da Zhen have contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China

    Zhao-Yang Wang, Zi-Da Zhen, Dong-Ying Fan, Pei-Gang Wang & Jing An

  2. Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, 100093, China

    Jing An

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  1. Zhao-Yang Wang
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  2. Zi-Da Zhen
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Contributions

ZY Wang designed and performed most of the experiments, analyzed the data, wrote and reviewed the manuscript. ZD Zhen performed flow cytometry experiments and TUNEL staining. DY Fan maintained cells, viruses, and reagents. PG Wang and J An conceived the project, analyzed the data, and finalized the manuscript.

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Correspondence to Pei-Gang Wang.

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The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

All institutional and national guidelines for the care and use of laboratory animals were followed, and all the animal experiments were approved by the Experimental Animal Welfare and Animal Ethics Committee of Capital Medical University, Beijing, China (permission code: AEEI-2015–048; permission date: April 20, 2015).

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Wang, ZY., Zhen, ZD., Fan, DY. et al. Axl Alleviates Neuroinflammation and Delays Japanese Encephalitis Progression in Mice. Virol. Sin. 36, 667–677 (2021). https://doi.org/10.1007/s12250-020-00342-y

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