Transcriptional profile of mice with good and poor spatial learning during West Nile virus recovery

Greater than 50% of patients who survive neuroinvasive West Nile virus (WNV), a mosquito-borne, positive-sense strand flavivirus, exhibit cognitive sequelae including memory impairments which may last several years. High survival rates from WNV neuroinvasive disease (WNND) (>90%) have led to hundreds to thousands of cases of WNV-mediated neurologic impairment accruing annually, yet underlying mechanisms responsible for these impairments have not been investigated. Here, we established a novel murine model of recovery from WNND in which intracranial inoculation of a mutant WNV (WNV-NS5-E218A) leads to rates of survival and cognitive dysfunction that mirror human WNND. WNV-NS5-E218A-recovered mice exhibit impaired spatial learning and persistently phagocytic microglia without significant loss of hippocampal neurons or brain volume. Whole transcriptome analysis of hippocampi from WNV-NS5-E218A-recovered mice with poor spatial learning was performed in order to identify target pathways and molecules underlying cognitive impairments during WNND recovery.