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Immunocytochemical evidence for Semliki Forest virus antigen persistence in mouse brain
A Khalili-Shirazi1, N Gregson, H E Webb
1United Medical Dental School, Guy's Hospital, London, U.K.
Abstract:
Semliki Forest virus (SFV) is neurotropic in mice. Mature virulent virus (strain L10) can be identified within the CNS by electron microscopy in adult mice. Inspite of high virus titres, avirulent SFV A7(74) cannot be visualised in the brain of adult mice. Immunocytochemical studies using monoclonal antibodies (MAbs) to A7(74) E1 and E2 proteins and viral envelope glycolipids, showed viral E1 to be labelled in the cerebral capillaries, the E2 and the putative envelope glycolipids were labelled in the cytoplasm of neurons, particularly in the hippocampal areas and glia in the cerebellum. By double labelling the presence of viral antigens in astrocytes and oligodendrocytes was demonstrated. Viral antigens were identified in the brain up to 183 days after infection. Paraffin sections from Bouin-fixed tissue were found to be the most suitable material for immunocytochemistry of SFV. The presence of life-long anti SFV antibody in the sera of animals after SFV infection, could be due to the persistence of viral antigens acting as constant stimuli to the immune system.
Insights
Semliki Forest virus (SFV) is neurotropic in mice. Immunocytochemistry revealed viral antigens in neurons and glial cells, persisting for months, potentially explaining lifelong immunity.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Semliki Forest virus (SFV) exhibits neurotropism in mice.
- Virulent SFV (strain L10) is detectable in the CNS, while avirulent SFV A7(74) is not by standard methods.
Purpose of the Study:
- To investigate the distribution and persistence of avirulent SFV A7(74) antigens in the mouse brain using immunocytochemistry.
- To correlate viral antigen presence with the host immune response.
Main Methods:
- Immunocytochemical studies using monoclonal antibodies against SFV E1 and E2 proteins.
- Double labeling techniques to identify viral antigens in specific brain cell types.
- Electron microscopy for visualization of virulent SFV.
Main Results:
- Viral E1 antigen localized to cerebral capillaries; E2 and envelope glycolipids found in neuronal cytoplasm (hippocampus) and cerebellar glia.
- Viral antigens detected in astrocytes and oligodendrocytes.
- Antigens persisted in the brain up to 183 days post-infection.
Conclusions:
- Avirulent SFV A7(74) antigens are present in specific neural and glial cells within the mouse CNS.
- The long-term persistence of viral antigens may act as a continuous stimulus, leading to lifelong anti-SFV antibody production.