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Updated: Aug 8, 2026
Viral Tracing of Genetically Defined Neural Circuitry
Published on: October 17, 2012
Basis of rabies virus neurovirulence in mice: expression of major histocompatibility complex class I and class II
D J Irwin1, W H Wunner, H C Ertl
1Department of Medicine, Queen's University, Kingston General Hospital, Ontario, Canada.
Abstract:
Expression of major histocompatibility complex (MHC) molecules on cells of the central nervous system (CNS) plays an important role in the pathogenesis of acute viral encephalitis. We have compared the induction of MHC class I and II mRNA transcripts in mice upon infection with the virulent challenge virus standard (CVS) strain of rabies virus and avirulent rabies virus variant RV194-2. Rabies virus antigen was detected with immunoperoxidase staining and 35S-labeled RNA probes were used to detect MHC class I and class II mRNA transcripts by in situ hybridization in infected brains. In CVS and RV194-2 infected animals, MHC class I mRNA expression occurred in the brain in neurons, glia, choroid plexus epithelial cells, ependymal cells, and inflammatory cells; expression was moderately higher in CVS-infected mice. In contrast, MHC class II mRNA expression was minimal in CVS-infected mice and it was markedly upregulated in CNS inflammatory cells upon RV194-2 infection. Both viruses induced an acute inflammatory reaction in the cerebrospinal fluid (CSF), which was more pronounced in CVS-infected mice. Both viruses also induced an antigen specific T and B cell response detectable in lymph nodes and spleen. These studies, which show a correlation between greater expression of MHC class II mRNA in the brain following intracerebral RV194-2 infection and protection against RV194-2 infection in the brain, suggest that recovery from avirulent rabies virus infection of neural cells involves T helper cells produced and/or retained in the brain for reasons that are not entirely clear.
Insights
Major histocompatibility complex (MHC) class II mRNA upregulation in the brain correlates with protection against avirulent rabies virus infection. This suggests T helper cells are crucial for recovery from neural rabies virus infections.
Area of Science:
- Neuroimmunology
- Virology
- Molecular Biology
Background:
- Major histocompatibility complex (MHC) molecules on central nervous system (CNS) cells are critical in acute viral encephalitis pathogenesis.
- Understanding differential immune responses to rabies virus strains is vital for encephalitis management.
Purpose of the Study:
- To compare MHC class I and II mRNA transcript induction in mouse brains infected with virulent (CVS) and avirulent (RV194-2) rabies virus strains.
- To investigate the role of MHC expression in the immune response and recovery from rabies virus infection.
Main Methods:
- Immunoperoxidase staining for rabies virus antigen detection.
- In situ hybridization using 35S-labeled RNA probes to detect MHC class I and II mRNA transcripts in infected brains.
- Analysis of inflammatory reactions in cerebrospinal fluid (CSF) and immune responses in lymph nodes and spleen.
Main Results:
- MHC class I mRNA was expressed in neurons, glia, and inflammatory cells in both CVS and RV194-2 infected mice, with higher levels in CVS infection.
- MHC class II mRNA expression was minimal in CVS infection but markedly upregulated in CNS inflammatory cells during RV194-2 infection.
- Both viruses induced acute inflammatory responses in CSF and antigen-specific T and B cell responses.
Conclusions:
- Greater MHC class II mRNA expression in the brain after RV194-2 infection correlates with protection.
- Recovery from avirulent rabies virus infection of neural cells likely involves T helper cells within the brain.
