Inflammatory responses in the nervous system of mice infected with a street isolate of rabies virus.
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.
Johnson
N
N
Veterinary Laboratories Agency (Weybridge), Surrey, Addlestone, United Kingdom. n.johnson2@vla.defra.gsi.gov.uk
Mansfield
K L
KL
Hicks
D
D
Nunez
A
A
Healy
D M
DM
Brookes
S M
SM
McKimmie
C
C
Fazakerley
J K
JK
Fooks
A R
AR
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D011818:Rabies / Q000276:immunology* / Q000473:pathology; D011820:Rabies virus / Q000472:pathogenicity / Q000502:physiology*; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology / Q000821:virology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral