Japanese Encephalitis Virus Infection Alters Both Neuronal and Astrocytic Differentiation of Neural Stem/Progenitor Cells

Abstract

Japanese encephalitis virus (JEV) predominantly infects neurons and causes damage to the central nervous system (CNS). Neural stem/progenitor cells (NSPCs) constitute multi-potent stem cell population in postnatal/adult brain, with capacity to differentiate into neurons, astrocytes or oligodendrocytes. NSPCs are known to play a pivotal role in CNS repair mechanisms during various neurological disorders. Previous studies from our laboratory have shown that JEV infection of NSPCs depletes the stem-cell pool, which may result in impaired repair functions leading to motor and cognitive deficits in survivors. In the present study, we evaluated the effect of JEV infection on differentiation potential of NSPCs isolated from BALB/c mouse pups (Post natal day 7). Results clearly indicated that, JEV infection was more robust in undifferentiated NSPCs as compared to differentiated ones. Further, JEV infected NSPCs showed hampered differentiation and arrested migration in adherent neurosphere cultures. Interestingly, the neuronal differentiation appeared to be more severely affected by JEV as compared to astrocyte differentiation. The transcription factors involved in both neuronal and astrocyte differentiations were significantly decreased upon JEV infection. Overall, results presented in this study comprehensively provide first evidence for JEV induced alteration of neuronal and astrocyte differentiation.