Abstract # 1862 Indoleamine-2,3-dioxgenase 1 (Ido1) protects against viral encephalitis

Abstract

Viral encephalitis (VE) is a life-threatening condition that can be triggered by infection with a multitude of different viruses including members of Picornaviridae. There are few treatment options for VE and the mechanisms that influence prognosis are poorly defined. Inhibition of Ido1 aids in viral clearance during experimental West Nile Virus encephalitis. To determine the role of Ido1 during picornavirus-induced encephalitis we inoculated wild-type (WT) and Ido1-/- mice with either vehicle or Theiler’s murine encephalomyelitis virus. Anxiety-like behavior was measured using an elevated zero maze at day 6 post-infection (p.i.). Burrowing activity was measured at days 4 and 6 p.i. Hippocampal gene expression was determined by RT-qPCR. Infected Ido1-/- mice showed a tendency toward a higher incidence of seizures (50% vs. 69.6%; p = 0.06). The occurrence of seizures was associated with greater time spent in the open areas of the maze, suggesting reduced anxiety. Infected Ido1-/- mice entered the light zone more often than WT mice. However, infection reduced burrowing activity and infected Ido1-/- mice burrowed less than WT mice. Infection increased Ido1, Ifng and viral RNA expression. The elevation in Ifng and viral RNA expression was greater in Ido1-/- compared to WT mice at day 8 p.i. These data indicate that Ido1 impedes viral replication, decreases neuroinflammation, and modulates encephalitis-induced behavioral alterations. Thus, the absence of Ido1 during picornavirus-induced encephalitis may be detrimental.