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Japanese Encephalitis Virus Infection Causes an Imbalance in the Activation of Mitochondrial Fusion/Fission Genes and Triggers the Activation of NOX2-mediated Oxidative Stress and Neuronal Cell Death

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Abstract

Mitochondria dysfunction may be an important contributor to Japanese encephalitis (JE) viral infection disease pathogenesis. In the current study, we define whether changes in mitochondrial DNA copy number (which is the biomarker for mitochondrial function) and alteration in mitochondria dynamics (fusion and fission) contribute to the pathology of the JE virus in vivo mice model. We found decreased mitochondria copy number, reduced activation of mitochondrial fission (FIS1/DRP1), and increased activation of mitochondrial fusion (MFN1/MFN2/OPA1) genes that are associated with increased NOX2-mediated ROS generation and neuronal cell death following JE virus infection. Furthermore, we found that antioxidant glutathione level decreases. In summary, the following study demonstrates that JE viral infection causes an imbalance in mitochondrial fission/fusion gene activation and promotes NOX2-mediated oxidative stress and cell death, suggesting that intervention in mitochondrial dynamics might be a potential therapeutic strategy for combating oxidative stress and inflammatory process in JE viral infection.

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Acknowledgements

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Funding

The following study was supported by the Ramalingaswami fellowship (BT/RLF/Re-entry/13/2014) from the Department of Biotechnology, Ministry of Science and Technology, Govt. of India and Grant-in-aid Scheme of the Department of Health Research (DHR-GIA) (R.11,013/66/2021-GIA/HR) to AK.

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  1. Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India

    Gajendra Singh & Alok Kumar

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  1. Gajendra Singh
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AK, GS: Conceptualization, Formal analysis, Investigation, Validation, Visualization, Writing an original draft, Methodology, Data curation. Both authors reviewed and edited the manuscript.

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Correspondence to Alok Kumar.

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Singh, G., Kumar, A. Japanese Encephalitis Virus Infection Causes an Imbalance in the Activation of Mitochondrial Fusion/Fission Genes and Triggers the Activation of NOX2-mediated Oxidative Stress and Neuronal Cell Death. Neurochem Res 48, 2196–2205 (2023). https://doi.org/10.1007/s11064-023-03898-9

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