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    • Keywords


      Atorvastatin; drug repurposing; Japanese encephalitis virus; neural stem/progenitor cell; neurotropic viruses; statins

    • Abstract


      Japanese encephalitis virus, a neurotropic flavivirus, causes sporadic encephalitis with nearly 25% fatal casereports. JEV infects neural stem/progenitor cells (NSPCs) and decreases their proliferation. Statin, a commonlyused class of cholesterol lowering drug, has been shown to possess potent anti-inflammatory and neuroprotectiveeffects in acute brain injury and chronic neurodegenerative conditions. Here, we aimed to check theefficacy of atorvastatin in alleviating the symptoms of Japanese encephalitis (JE). Using BALB/c mouse modelof 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 activationand production of proinflammatory cyto/chemokine production post JEV infection in vivo. It alsoreduced interferon-beta response in the neurogenic environs. The neuroprotective role of atorvastatin is againevident from the rescued neurosphere size and decreased cell death in vitro. It has also been observed that uponatorvastatin administration, cell cycle regulatory proteins and cell survival proteins are also restored to theirrespective expression level as observed in uninfected animals. Thus the antiviral, immunomodulatory andneuroprotective roles of atorvastatin reflect in our experimental observations. Therefore, this drug broadens apath for future therapeutic measures against JEV infection.

    • Author Affiliations



      1. National Brain Research Centre, Manesar, Gurugram 122 052, India
      2. Present Address: Institute for Stem Cell Science and Regenerative Medicine, Bengaluru 560 065, India
      3. Present Address: Department of Pharmacology and Physiology, Pavilion Roger-Gaudry, Universite de Montre´al, Montre´al, Que´bec H3T 1J4, Canada
      4. Present Address: Tulane National Primate Research Center, 18703, Three Rivers Road, Covington, Louisiana 70433, USA
      5. Present Address: Department of Molecular Medicine, Faculty of Medicine, Universite´ Laval, Que´bec G1V 4G2, Canada
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