Temporal analyses of the neuropathogenesis of a West Nile virus infection in mice

A West Nile virus (WNV) infection in humans can produce neurological symptoms including acute flaccid paralysis, encephalitis, meningitis and myelitis. To investigate the pathogenesis of WNV in the peripheral and the central nervous system (PNS and CNS), the authors used a murine footpad inoculation model of WNV infection. Survival curves of virus-infected animals of ages 4- to 6-weeks-old demonstrated age-dependent mortality where older animals (6-weeks-old) had a higher mortality rate compared to younger animals (4- and 5-weeks-old). The mice that survived the virus infection formed WNV-reactive antibodies, confirming viral infection and clearance. The localization of viral RNA (vRNA) and antigen in infected murine tissues was investigated using TaqMan and immunohistochemistry (IHC) respectively. During a nine day infection, vRNA levels in the spinal cord and brainstem fluctuated, suggesting early viral clearance from these tissues by days 3-4 p.i. with later re-introduction. Viral antigens detected using IHC were primarily observed in three main regions of the brain: cortex, hippocampus and brainstem. Additionally, the dorsal root ganglion neurons of the PNS stained positive for viral antigens. These data are consistent with multiple routes of neuroinvasion following a peripheral inoculation of virus and do not preclude the previous observation that virus-infected peripheral neurons can introduce virus into the CNS by a retrograde transport mechanism.