Targeting src Homology 2-Containing Inositol Phosphatase-1 (SHIP1)

25 MicroRNAs (miRNAs) are single stranded small RNA molecules that regulate various cellular 26 processes. miR-155 regulates various aspects of innate and adaptive immune response and plays 27 a key role in various viral infections and resulting neuroinflammation. In the present study, 28 evaluated the involvement of miR-155 in modulating Japanese Encephalitis Virus (JEV)29 induced neuroinflammation. We observed that miR-155 expression was up regulated during JEV 30 infection of mouse primary microglia, BV-2 microglia cell line, and in both mouse and human 31 brain. In vitro and in vivo knockdown of miR-155 minimized JEV-induced inflammatory 32 responses. In the present study, we confirmed targeting of SHIP1 3'UTR by miR-155 in the 33 context of JEV infection. Inhibition of SHIP1 by miR-155 resulted in higher interferon beta 34 (IFN) and pro-inflammatory cytokine production through activation of TANK-binding kinase 35 1 (TBK-1). Based on these observations we conclude that miR-155 modulates 36 neuroinflammatory response during JEV infection via negative regulation of SHIP1 expression. 37 Thus, modulation of miR-155 could be a novel strategy to regulate JEV induced 38 neuroinflammation. 39