Early gene activation initiates neuroinflammation prior to VSV neuroinvasion: Impact on antiviral responses and sleep

J Neuroimmunol. 2017 Feb 15;303:31-42. doi: 10.1016/j.jneuroim.2016.12.002. Epub 2016 Dec 29.

Abstract

Rapid eye movement (REM) sleep is rapidly and persistently suppressed during vesicular stomatitis virus (VSV) encephalitis in C57Bl/6J (B6) mice. REM sleep suppression was associated with a complex global brain chemokine/cytokine response with bimodal kinetics although regionally distinct cytokine profiles were readily identified. Cytokine mRNA was translated either immediately or suppressed until the pathogen was cleared from the CNS. Innate signaling pathway (TLRs, RIG-I) activation occurred rapidly and sequentially prior to VSV neuroinvasion suggesting that antiviral states are quickly established in the CNS in advance of viral pathogen penetration. Il1β suppressed REM sleep mimicking aspects of VSV-induced sleep alterations whereas some robustly induced chemokines may be protective of REM. Thus, multiple brain chemokines may mediate sleep across VSV encephalitis via differential somnogenic effects.

Keywords: Cytokine; Innate signaling pathways; Neuroinflammation; Sleep; Temporal gene regulation; Vesicular stomatitis virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / immunology*
  • Brain / metabolism
  • Brain / virology
  • Encephalitis, Viral / immunology*
  • Encephalitis, Viral / metabolism
  • Gene Regulatory Networks / genetics
  • Gene Regulatory Networks / immunology
  • Inflammation Mediators / immunology*
  • Inflammation Mediators / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Sleep, REM / genetics
  • Sleep, REM / immunology*
  • Transcriptional Activation / genetics
  • Transcriptional Activation / immunology*
  • Vesicular stomatitis Indiana virus / immunology*

Substances

  • Inflammation Mediators