Single cell molecular dynamics in brains of mice infected with West Nile virus

West Nile virus (WNV) is a vector-borne neurotropic flavivirus spread by mosquitos and birds. WNV can lead to encephalitis or meningitis causing permanent damage to the central nervous system or death in ~1% of infected individuals. The virus infects ~10,000 individuals annually in Israel, resulting in ~80 hospitalizations due to neurological complications and ~10 deaths. Despite the clinical importance to public health, studies investigating WNV infection in the brain are limited and do not include a thorough investigation of in-vivo brain cell dynamics following infection. In this study, we utilized WNV as a neurotropic prototype virus to systematically characterize, for the first time, the response of different brain cell populations to a neuronal infection, at the single cell level. Mice were infected with WNV, brains were harvested and dissociated into single cells at different time points following infection, and single cell RNA sequencing via 10X genomics technology was performed. Subsequent bioinformatics analysis characterized the genes and pathways altered by infection at each time point per each cell type identified. Results will be validated via qRT-PCR in combination with protein assay analyses. These discoveries will set the basis for targeting and/or attenuating the clinical manifestations caused by infection with WNV and other neurotropic viruses.