Persistence of virus-specific immune responses in the central nervous system of mice after West Nile virus infection

Immunocompetent, adult mice were inoculated subcutaneously with WNV, and the CNS immune response was examined at 1, 2, 4, 8, 12 and 16 weeks post-inoculation (wpi). Characterization of lymphocyte phenotypes in the CNS revealed elevation of CD19+ B cells for 4 wpi, CD138 plasma cells at 12 wpi, and CD4+ and CD8+ T cells for at least 12 wpi. T cells recruited to the brain were activated, and regulatory T cells (Tregs) were present for at least 12 wpi. WNV-specific antibody secreting cells were detected in the brain from 2 to 16 wpi, and virus-specific CD8+ T cells directed against an immunodominant WNV epitope were detected in the brain from 1 to 16 wpi. Furthermore, these WNV-specific immune responses occurred in mice with and without acute clinical disease.Virus-specific immune cells persist in the CNS of mice after WNV infection for up to 16 wpi.West Nile virus (WNV), a member of the family Flaviviridae, is a positive-sense, single-stranded RNA virus, which is maintained in a mosquito-bird enzootic cycle. Upon incidental infection with WNV, approximately 20% of humans experience a self-limiting illness called "West Nile fever", and less than 1% develop West Nile neuroinvasive disease (WNND) [1]. WNND is characterized by encephalitis, myelitis, and/or meningitis and can lead to death [2-4]. In addition to acute disease, long term sequelae occur in individuals recovering from West Nile fever and WNND [3,5-8]. The underlying mechanisms resulting in these sequelae remain unclear, but may partly be due to viral persistence.Several studies provide evidence for persistence of WNV in humans. WNV RNA persists in urine of convalescent patients for as long as 6.7 years after disease onset [9]. In blood donors, WNV RNA is detected in blood as long as 104 days after index donation [10]. WNV-specific immunoglobulin M (IgM) persists in serum of patients with West Nile disease and WNV-positive blood donors for as long as 11 to 16 months [10-13]. In addition, IgM persists in cerebr