Inflammatory responses in the nervous system of mice infected with a street isolate of rabies virus

N. Johnson, K. L. Mansfield, D. Hicks, A. Nunez, D. M. Healy, S. M. Brookes, C. McKimmie, J. K. Fazakerley, A. R. Fooks

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Rabies virus causes severe encephalitis that is invariably fatal for the victim. However, the contribution of the virus and the host to damage of the CNS is unclear. In order to investigate this we studied the neuropathology and CNS gene expression patterns in a murine model of rabies using a 'street' isolate RV61. This virus was derived from a human case of disease. In this model, infection of the CNS progresses rapidly following inoculation in the periphery, leading to extensive virus replication in the brain and the development of disease. However, previous studies have found little evidence of inflammation and lymphocyte infiltration in many regions of the CNS of infected mice. During the current study virus replication was detected in the dorsal root ganglia (DRG), spinal cord, brain and salivary gland at 11 days postinfection (dpi). Mononuclear cell infiltration was observed in the DRG and to a lesser extent, the spinal cord. Immunolabelling demonstrated that T-lymphocytes were the dominant population of infiltrating cells. Murine innate immune response gene transcripts were detected in the brain as early as 5 dpi. At 11 dpi, coincidentwith the onset of disease, elevated levels of mRNA transcripts were recorded for type-1 (alpha and beta) and type-2 interferon (gamma) and certain chemokines (CCL5 and CXCL10) with chemotactic properties for T-cells. We suggest that damage to the DRG and spinal cord could be due to a combination of both virus infection and the infiltration of T-cells.
Original languageEnglish
Title of host publicationTowards the Elimination of Rabies in Eurasia: Joint OIE/WHO/EU International Conference, Paris, May 2007: Proceedings
EditorsB. Dodet, A. R. Fooks, T. Muller, N. Tordo
Place of PublicationVeterinary Laboratories Agency (Weybridge), Surrey, Addlestone, United Kingdom. n.johnson2@vla.defra.gsi.gov.uk
PublisherKarger
Pages65-72
Number of pages8
ISBN (Print)978-3-8055-8550-7
Publication statusPublished - 2008
EventJoint OIE/WHO/EU International Conference - Paris, France
Duration: 27 May 200730 May 2007

Publication series

NameDevelopments in Biologicals
Volume131

Conference

ConferenceJoint OIE/WHO/EU International Conference
CountryFrance
CityParis
Period27/05/0730/05/07

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