A tick-borne encephalitis model in infant rats infected with langat virus

Maffioli, Carola; Grandgirard, Denis; Engler, Olivier; Leib, Stephen (2014). A tick-borne encephalitis model in infant rats infected with langat virus. Journal of neuropathology and experimental neurology, 73(12), pp. 1107-1115. Lippincott Williams & Wilkins 10.1097/NEN.0000000000000131

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Tick-borne encephalitis virus (TBEV) is the causative agent of human TBE, a severe infection that can cause long-lasting neurologic sequelae. Langat virus (LGTV), which is closely related to TBEV, has a low virulence for human hosts and has been used as a live vaccine against TBEV. Tick-borne encephalitis by natural infection of LGTV in humans has not been described, but one of 18,500 LGTV vaccinees developed encephalitis. The pathogenetic mechanisms of TBEV are poorly understood and, currently, no effective therapy is available. We developed an infant rat model of TBE using LGTV as infective agent. Infant Wistar rats were inoculated intracisternally with 10 focus-forming units of LGTV and assessed for clinical disease and neuropathologic findings at Days 2, 4, 7, and 9 after infection. Infection with LGTV led to gait disturbance, hypokinesia, and reduced weight gain or weight loss. Cerebrospinal fluid concentrations of RANTES, interferon-γ, interferon-β, interleukin-6, and monocyte chemotactic protein-1 were increased in infected animals. The brains of animals with LGTV encephalitis exhibited characteristic perivascular inflammatory cuffs and glial nodules; immunohistochemistry documented the presence of LGTV in the thalamus, hippocampus, midbrain, frontal pole, and cerebellum. Thus, LGTV meningoencephalitis in infant rats mimics important clinical and histopathologic features of human TBE. This new model provides a tool to investigate disease mechanisms and to evaluate new therapeutic strategies against encephalitogenic flaviviruses.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Maffioli, Carola; Grandgirard, Denis and Leib, Stephen

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0022-3069

Publisher:

Lippincott Williams & Wilkins

Funders:

[4] Swiss National Science Foundation
[UNSPECIFIED] Swiss Federal Office for Civil Protection (Research Contract No. 353001545)

Language:

English

Submitter:

Stephen Leib

Date Deposited:

27 Jan 2015 13:33

Last Modified:

08 Feb 2017 14:42

Publisher DOI:

10.1097/NEN.0000000000000131

PubMed ID:

25383637

BORIS DOI:

10.7892/boris.61930

URI:

https://boris.unibe.ch/id/eprint/61930

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