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

- VSV neuroinvasion induced a robust and complex global brain cytokine response with bimodal kinetics.
- Brain cytokine profiles were regionally restricted and generally unrelated to peripheral responses.
- A discordance between cytokine mRNA synthesis and translation occurred for CXCL10 and OPN.
- Temporally regulated Innate signaling activation occurred prior to and coincident with VSV neuroinvasion.
- Il-1, but not several induced chemokines, replicated VSV-induced REM sleep suppression.

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.

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