Type I interferon signaling limits reoviral tropism within the brain and prevents lethal systemic infection

Kalen R. Dionne, John M. Galvin, Stephanie A. Schittone, Penny Clarke, Kenneth L. Tyler

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

In vivo and ex vivo models of reoviral encephalitis were utilized to delineate the contribution of type I interferon (IFN) to the host's defense against local central nervous system (CNS) viral infection and systemic viral spread. Following intracranial (i.c.) inoculation with either serotype 3 (T3) or serotype 1 (T1) reovirus, increased expression of IFN-α, IFN-β, and myxovirus-resistance protein (Mx1; a prototypical IFN stimulated gene) was observed in mouse brain tissue. Type I IFN receptor deficient mice (IFNAR -/-) had accelerated lethality, compared to wildtype (B6wt) controls, following i.c. T1 or T3 challenge. Although viral titers in the brain and eyes of reovirus infected IFNAR -/- mice were significantly increased, these mice did not develop neurologic signs or brain injury. In contrast, increased reovirus titers in peripheral tissues (liver, spleen, kidney, heart, and blood) of IFNAR -/- mice were associated with severe intestinal and liver injury. These results suggest that reovirus-infected IFNAR -/- mice succumb to peripheral disease rather than encephalitis per se. To investigate the potential role of type I IFN in brain tissue, brain slice cultures (BSCs) were prepared from IFNAR -/ mice and B6wt controls for ex vivo T3 reovirus infection. Compared to B6wt controls, reoviral replication and virusinduced apoptosis were enhanced in IFNAR -/- BSCs indicating that a type I IFN response, initiated by resident CNS cells, mediates innate viral immunity within the brain. T3 reovirus tropism was extended in IFNAR -/- brains to include dentate neurons, ependymal cells, and meningeal cells indicating that reovirus tropism within the CNS is dependent upon type I interferon signaling.

Original languageEnglish
Pages (from-to)314-326
Number of pages13
JournalJournal of NeuroVirology
Volume17
Issue number4
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Keywords

  • Brain
  • Encephalitis
  • Interferon
  • Reovirus
  • Tropism
  • Virus

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