Clearance of Attenuated Rabies Virus from Brain Tissues is Required for Long-Term Protection Against CNS Challenge with a Pathogenic Variant
| Autor: | Samantha Garcia, Rhonda B. Kean, Aurore Lebrun, D. Craig Hooper |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Rabies viruses Biology medicine.disease_cause Vaccines Attenuated Virus Article 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Immune system Virology medicine Animals Neurovirology Lyssavirus Attenuated vaccine Rabies virus Brain biology.organism_classification Mice Inbred C57BL 030104 developmental biology Neurology Immunization Rabies Vaccines Neurology (clinical) 030215 immunology |
| Popis: | Rabies virus is a neurotropic lyssavirus which is 100% fatal in its pathogenic form when reaching unprotected CNS tissues. Death can be prevented by mechanisms delivering appropriate immune effectors across the blood-brain barrier which normally remains intact during pathogenic rabies virus infection. One therapeutic approach is to superinfect CNS tissues with attenuated rabies virus which induces blood-brain barrier permeability and immune cell entry. Current thinking is that peripheral rabies immunization is sufficient to protect against a challenge with pathogenic rabies virus. While this is undoubtedly the case if the virus is confined to the periphery, what happens if the virus reaches the CNS is less well-understood. In the current study, we find that peripheral immunization does not fully protect mice long-term against an intranasal challenge with pathogenic rabies virus. Protection is significantly better in mice that have cleared attenuated virus from the CNS and is associated with a more robust CNS recall response evidently due to the presence in CNS tissues of elevated numbers of lymphocytes phenotypically resembling long-term resident immune cells. Adoptive transfer of cells from rabies-immune mice fails to protect against CNS challenge with pathogenic rabies virus further supporting the concept that long-term resident immune cell populations must be established in brain tissues to protect against a subsequent CNS challenge with pathogenic rabies virus. |
| Databáze: | OpenAIRE |
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