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The pathogenicity of louping ill virus for mice and lambs
B J Sheahan1, M Moore, G J Atkins
1Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Dublin, Ballsbridge, Dublin 4, Ireland.
Abstract:
Mice and lambs were infected with the LI/I, LI/31 or MA54 strain of louping ill virus (LIV) to provide information relevant to testing the efficacy and biosafety of a new generation of flavivirus vaccines based on a Semliki Forest virus (SFV) vector. Whereas clinical signs and neuropathological lesions were consistently severe in mice, the majority of lambs showed lesions of moderate severity and only lambs with severe lesions were clinically affected. For both species, dispersal of viral antigen occurred along neuronal cell processes, and neuronal degeneration and death were confirmed as central events after infection with LIV. In contrast to lambs, in which most lesions remained localized, mice showed widely dispersed lesions which were associated with less intense leucocytic infiltrates. Among the infiltrating cells, histiocytes predominated and apoptotic forms were prominent in severely affected animals. The intranasal route of infection provided an efficient avenue for entry of LIV into the brain and resulted in lesions which were more severe than those produced by subcutaneous or intraperitoneal inoculation.
Insights
Louping ill virus (LIV) infection causes severe neuropathology in mice but moderate lesions in lambs. Intranasal infection efficiently targets the brain, highlighting viral pathogenesis for vaccine development.
Area of Science:
- Veterinary Virology
- Neuroscience
- Immunology
Background:
- Louping ill virus (LIV) is a tick-borne flavivirus causing neurological disease.
- Developing effective flavivirus vaccines, particularly those using Semliki Forest virus (SFV) vectors, requires understanding LIV pathogenesis.
- Assessing vaccine efficacy and biosafety necessitates robust animal models that mimic human disease.
Purpose of the Study:
- To investigate the neuropathology and viral antigen distribution of Louping ill virus (LIV) in mice and lambs.
- To compare disease severity and lesion localization between species following LIV infection.
- To evaluate the intranasal route as an efficient infection pathway for LIV neuroinvasion.
Main Methods:
- Mice and lambs were infected with three strains of LIV (LI/I, LI/31, MA54).
- Clinical signs, neuropathological lesions, and viral antigen distribution were assessed.
- Different inoculation routes (intranasal, subcutaneous, intraperitoneal) were compared.
Main Results:
- Mice exhibited consistently severe clinical signs and neuropathology; lambs showed moderate lesions, with severe clinical signs only in affected lambs.
- Viral antigen spread along neuronal processes, leading to neuronal degeneration and death in both species.
- Mice displayed widespread lesions, while lambs had more localized lesions; histiocytes and apoptotic cells predominated in mice.
- Intranasal infection resulted in more severe brain lesions than other routes.
Conclusions:
- LIV infection causes significant neuroinflammation and neuronal damage, with species-specific differences in lesion severity and distribution.
- The intranasal route is highly effective for LIV neuroinvasion, suggesting its importance in natural transmission.
- These findings provide crucial insights for developing and testing novel flavivirus vaccines, particularly SFV-vectored vaccines, using appropriate animal models.