Global Analysis of Host-Encoded Circular RNAs Reveals their Potential Role in Regulating the West Nile Virus-Induced Neuroinflammation

West Nile virus (WNV)-associated encephalitis is characterized by glial cell-mediated rampant production of inflammatory cytokines which in turn contributes to neuronal cell damage. Circular RNAs (circRNAs) have recently been emerged as a new class of back-spliced non-coding RNAs that regulate gene expression by sponging microRNAs (miRNAs), and thus, cause a substantial impact on various biological processes, including the brain pathophysiology. However, it remains unknown how circRNAs regulate WNV-induced neuroinflammation. By employing high-throughput RNA-sequencing technology, we found 16,924 circRNAs and 254 miRNAs significantly differentially regulated in WNV-infected mice brains. The biological function and pathway annotation analyses exhibited that the differentially expressed circRNAs and miRNAs were mainly enriched to immune and inflammatory responses. The established circRNA-miRNA co-expression network suggested an inverse circRNA2068-miRNA-24 correlation in regulating the WNV-induced neuroinflammation. The predicted inverse correlation between circRNA2068 and miRNA-24 was experimentally validated by inhibiting/overexpressing these RNA entities. In addition, the silencing of circRNA2068 or overexpression of miRNA-24 resulted in a reduced production of inflammatory cytokines upon WNV infection of mouse primary neuron/glia. In conclusion, we presented the first transcriptomic landscape of circRNAs in mice brain tissues infected with WNV. Our data provide deeper insights into the host response to WNV infection and suggest the circRNA-targeting therapeutic options to treat the WNV-mediated encephalitis.