Neuronal destruction and CNS inflammation are enhanced in WNV infected IPS-1 2/2 mice To determine the role of the RLR pathway in protection of neurons against WNV pathogenesis in vivo, we conducted histological analysis of brain tissue from wild type and IPS-1 2/2 mice infected with WN-TX ( Fig 4A) . Analysis of brain sections from infected wild type mice revealed little or no inflammation or neuronal damage, with sparse and focal cell infiltrates restricted to the hippocampus and cerebral cortex on day 6 pi. By day 10 pi (a timepoint in wild type mice in which peak virus replication in the CNS occurs [34] ) cellular infiltrates were present in the parenchyma and neuronal destruction was observed throughout the cortex and hippocampus. In contrast, brain sections from infected IPS-1 2/2 mice recovered on day 6 pi displayed extensive injury to neurons in the cortex and granular neurons of the hippocampus. Damaged neurons appeared pyknotic with vacuolation, degeneration and cell dropout. Somewhat surprisingly, we observed extensive inflammation in the brains from infected IPS-1 2/2 mice within the cortex, hippocampus, and cerebellum (data not shown) displaying prominent perivascular and parenchymal immune cell infiltrates.