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

• Published in: Journal of neuroimmunology 2017-02, Vol.303, p.31-42
• Main Authors: Ciavarra, Richard P, Lundberg, Patric, Machida, Mayumi, Ambrozewicz, Marta A, Wellman, Laurie L, Breving, Kimberly, Steel, Christina, Sanford, Larry D
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Brain - immunology; Brain - metabolism; Brain - virology; Cytokine; Encephalitis, Viral - immunology; Encephalitis, Viral - metabolism; Gene Regulatory Networks - genetics; Gene Regulatory Networks - immunology; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Innate signaling pathways; Male; Mice; Mice, Inbred C57BL; Neuroinflammation; Neurology; Sleep; Sleep, REM - genetics; Sleep, REM - immunology; Temporal gene regulation; Transcriptional Activation - genetics; Transcriptional Activation - immunology; Vesicular stomatitis Indiana virus - immunology; Vesicular stomatitis virus
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2016.12.002

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.