Japanese encephalitis virus (JEV) can invade the central nervous system, and consequently induce neuroinflammation, which is characterized by profound neuronal cells damage accompanied by astrogliosis and microgliosis. Albeit microRNAs (miRNAs) have emerged as major regulatory non-coding RNAs with profound effects on inflammatory response, it is unknown how astrocytic miRNAs regulate JEV-induced inflammation. Here, we found the involvement of miR-19b-3p in regulating JEV-induced inflammatory responsein vitroandin vivo. The data demonstrated that miR-19b-3p is up-regulated in cultured cells and mice brain tissues during JEV infection. Overexpression of miR-19b-3p led to increased production of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-1β, and chemokine (C-C motif) ligand 5, after JEV infection, whereas knockdown of miR-19b-3p had completely opposite effects. Mechanistically, miR-19b-3p modulated the JEV-induced inflammatory response via targeting ring finger protein 11, a negative regulator of nuclear factor-kappa B signaling. We also found that inhibition of ring finger protein 11 by miR-19b-3p resulted in accumulation of nuclear factor-kappaB in the nucleus, which in turn led to higher production of inflammatory cytokines.In vivosilencing of miR-19b-3p by specific antagomir reinvigorates expression level of RNF11, which in turn reduces the production of inflammatory cytokines, vitiates gliosis and neuronal cell death, and eventually improves survival rate in the mouse model. Collectively, our results demonstrate that miR-19b-3p positively regulates JEV-induced inflammatory response. Thus, miR-19b-3p targeting may constitute a thought-provoking approach to rein in JEV-induced inflammation.
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