Mortality following peripheral infection with tick-borne encephalitis virus results from a combination of central nervous system pathology, systemic inflammatory and stress responses

Hayasaka, Daisuke; Nagata, Noriyo; Fujii, Yoshiki; Hasegawa, Hideki; Sata, Tetsutaro; Suzuki, Ryuji; Gould, Ernest A.; Takashima, Ikuo; Koike, Satoshi. 2009 Mortality following peripheral infection with tick-borne encephalitis virus results from a combination of central nervous system pathology, systemic inflammatory and stress responses. Virology, 390. 139-150. 10.1016/j.virol.2009.04.026

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Abstract/Summary

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 (N107 PFU), mice started to die early (8 days) and mortality rates reached N80%. These doses induced acute and widespread infection of the CNS. On the other hand, following subcutaneous infection with low challenge doses (102–106 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-α 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.

Item Type:	Publication - Article
Digital Object Identifier (DOI):	10.1016/j.virol.2009.04.026
Programmes:	CEH Topics & Objectives 2009 - 2012 > Biodiversity > BD Topic 2 - Ecological Processes in the Environment
UKCEH and CEH Sections/Science Areas:	Hails
ISSN:	0042-6822
Additional Keywords:	Tick-borne encephalitis virus, mouse model, mortality, peripheral infection, central nervous system pathology, systemic inflammation, systemic stress response
NORA Subject Terms:	Biology and Microbiology
Date made live:	14 Apr 2010 08:48 +0 (UTC)
URI:	https://nora.nerc.ac.uk/id/eprint/9226

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