title: Mortality following peripheral infection with tick-borne encephalitis virus results from a combination of central nervous system pathology, systemic inflammatory and stress responses.
abstract: Tick-borne encephalitis virus (TBEV) induces acute central nervous system (CNS) disease in humans. In this study, we investigate the pathogenetic mechanisms that correlate with fatal infection with TBEV in a mouse model. Following subcutaneous infection with high challenge doses (>10(7) PFU), mice started to die early (8 days) and mortality rates reached >80%. These doses induced acute and widespread infection of the CNS. On the other hand, following subcutaneous infection with low challenge doses (10(2)-10(6) PFU), mice started to die late (11 days) and approximately one half of the mice survived but exhibited degrees of encephalitis similar to dying mice. However, low dose dying mice exhibited severe systemic stress response, and increased levels of TNF-alpha compared with recovering mice. We therefore conclude that in addition to the development of CNS disease, systemic inflammatory and stress responses contribute to induce a fatal infection following subcutaneous infection of mice with TBEV.
authors.affiliation: Department of Microbiology and Immunology, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan. hayasaka-ds@igakuken.or.jp
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hayasaka
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Fujii
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Ryuji
authors.initials: R
authors.lastname: Suzuki
authors.forename: Ernest A
authors.initials: EA
authors.lastname: Gould
authors.forename: Ikuo
authors.initials: I
authors.lastname: Takashima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Koike
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000473:pathology; D004669:Encephalitis Viruses, Tick-Borne / Q000472:pathogenicity* / Q000502:physiology; D004675:Encephalitis, Tick-Borne / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D013312:Stress, Physiological; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014779:Virus Replication
chemical_list: D014409:Tumor Necrosis Factor-alpha