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Atorvastatin ameliorates viral burden and neural stem/progenitor cell (NSPC) death in an experimental model of Japanese encephalitis

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Abstract

Japanese encephalitis virus, a neurotropic flavivirus, causes sporadic encephalitis with nearly 25% fatal case reports. JEV infects neural stem/progenitor cells (NSPCs) and decreases their proliferation. Statin, a commonly used class of cholesterol lowering drug, has been shown to possess potent anti-inflammatory and neuroprotective effects in acute brain injury and chronic neurodegenerative conditions. Here, we aimed to check the efficacy of atorvastatin in alleviating the symptoms of Japanese encephalitis (JE). Using BALB/c mouse model of JEV infection, we observed that atorvastatin effectively reduces viral load in the subventricular zone (SVZ) of infected pups and decreases the resultant cell death. Furthermore, atorvastatin abrogates microglial activation and production of proinflammatory cyto/chemokine production post JEV infection in vivo. It also reduced interferon-β response in the neurogenic environs. The neuroprotective role of atorvastatin is again evident from the rescued neurosphere size and decreased cell death in vitro. It has also been observed that upon atorvastatin administration, cell cycle regulatory proteins and cell survival proteins are also restored to their respective expression level as observed in uninfected animals. Thus the antiviral, immunomodulatory and neuroprotective roles of atorvastatin reflect in our experimental observations. Therefore, this drug broadens a path for future therapeutic measures against JEV infection.

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Abbreviations

ATR:

atorvastatin

JEV:

Japanese encephalitis virus

NSPC:

neural stem/progenitor cell

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Acknowledgements

The study is supported by research grant to AB form Department of Biotechnology (BT/PR27796/Med/29/1301/2018). AB is also the recipient of Tata Innovation Fellowship (BT/HRD/35/01/02/2014). SM (Mallick) is also recipient of grant from Science & Engineering Research Board (SERB) (PDF/2016/000440). The authors sincerely acknowledge the help of Kanhaiya Lal Kumawat and Manish Dogra.

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Author notes

  1. Masood Ahmad Wani

    Present address: Institute for Stem Cell Science and Regenerative Medicine, Bengaluru, 560 065, India

  2. Sriparna Mukherjee

    Present address: Department of Pharmacology and Physiology, Pavilion Roger-Gaudry, Université de Montréal, Montréal, Québec, H3T 1J4, Canada

  3. Suvadip Mallick

    Present address: Tulane National Primate Research Center, 18703, Three Rivers Road, Covington, Louisiana, 70433, USA

  4. Irshad Akbar

    Present address: Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, G1V 4G2, Canada

Authors and Affiliations

  1. National Brain Research Centre, Manesar, Gurugram, 122 052, India

    Masood Ahmad Wani, Sriparna Mukherjee, Suvadip Mallick, Irshad Akbar & Anirban Basu

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  1. Masood Ahmad Wani
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Correspondence to Anirban Basu.

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Corresponding editor: Saumitra Das

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Wani, M.A., Mukherjee, S., Mallick, S. et al. Atorvastatin ameliorates viral burden and neural stem/progenitor cell (NSPC) death in an experimental model of Japanese encephalitis. J Biosci 45, 77 (2020). https://doi.org/10.1007/s12038-020-00052-3

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