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Isolation of Brain-infiltrating Leukocytes
Published on: June 13, 2011
Peripheral immunization blocks lethal actions of vesicular stomatitis virus within the brain
Koray Ozduman1, Guido Wollmann, Sebastian A Ahmadi
1Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
Journal of Virology
|September 4, 2009
Summary
Attenuated vesicular stomatitis virus (VSV) variants show reduced neurovirulence. Peripheral immunization effectively prevents lethal VSV brain infections, highlighting potential for safer VSV-based therapies.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Vesicular stomatitis virus (VSV) is a rhabdovirus with potential as a vaccine vector and oncolytic virus.
- VSV brain infection can cause severe neurological impairment or death.
- Developing safer VSV variants for therapeutic use is crucial.
Purpose of the Study:
- To compare the neuroinvasiveness and neuromorbidity of wild-type VSV and two attenuated VSV strains (VSV-CT1 and VSV-CT9-M51).
- To evaluate the efficacy of peripheral immunization in preventing lethal VSV brain infections.
Main Methods:
- Direct injection of VSV variants into the mouse brain.
- Intranasal inoculation of young mice with VSV variants.
- Peripheral immunization (intranasal or intramuscular) followed by VSV challenge.
- Assessment of neuroinvasiveness, neuromorbidity, and neuropathology.
Main Results:
- Wild-type VSV caused lethal encephalitis upon direct brain injection, while attenuated strains showed partial survival.
- Attenuated VSV strains exhibited significantly reduced neuroinvasiveness after intranasal inoculation.
- VSV-CT9-M51 demonstrated the lowest neuropathology and could target glioblastoma in the brain.
- Peripheral immunization with VSV variants completely prevented lethal effects of subsequent VSV brain injections.
Conclusions:
- Attenuated VSV strains possess reduced neurovirulence compared to wild-type VSV.
- Peripheral immunization is a highly effective strategy to block the lethal neurotoxic effects of VSV infection.
- These findings support the development of attenuated VSV for safer therapeutic applications.
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