title: Early gene activation initiates neuroinflammation prior to VSV neuroinvasion: Impact on antiviral responses and sleep.
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.
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23501, United States. Electronic address: ciavarrp@evms.edu.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Ciavarra
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23501, United States.
authors.forename: Patric
authors.initials: P
authors.lastname: Lundberg
authors.affiliation: Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23501, United States.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Machida
authors.affiliation: Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23501, United States.
authors.forename: Marta A
authors.initials: MA
authors.lastname: Ambrozewicz
authors.affiliation: Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23501, United States.
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Wellman
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23501, United States.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Breving
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23501, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: Steel
authors.affiliation: Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23501, United States.
authors.forename: Larry D
authors.initials: LD
authors.lastname: Sanford
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018792:Encephalitis, Viral / Q000276:immunology* / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012895:Sleep, REM / Q000235:genetics / Q000276:immunology*; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators
keywords: Cytokine; Innate signaling pathways; Neuroinflammation; Sleep; Temporal gene regulation; Vesicular stomatitis virus