A Transgenic Mouse Model of Poliomyelitis
Satoshi Koike1, Noriyo Nagata2
1Neurovirology Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan. koike-st@igakuken.or.jp.
Abstract:
Transgenic mice (tg mice) that express the human poliovirus receptor (PVR), CD155, are susceptible to poliovirus and develop a neurological disease that resembles human poliomyelitis. Assessment of the neurovirulence levels of poliovirus strains, including mutant viruses produced by reverse genetics, circulating vaccine-derived poliovirus, and vaccine candidates, is useful for basic research of poliovirus pathogenicity, the surveillance of circulating polioviruses, and the quality control of oral live poliovirus vaccines, and does not require the use of monkeys. Furthermore, PVR-tg mice are useful for studying poliovirus tissue tropism and host immune responses. PVR-tg mice can be bred with mice deficient in the genes involved in viral pathogenicity. This report describes the methods used to analyze the pathogenicity and immune responses of poliovirus using the PVR-tg mouse model.
Insights
Transgenic mice expressing the human poliovirus receptor (PVR) offer a monkey-free model for studying poliovirus pathogenicity and immune responses. This PVR-tg mouse model aids in neurovirulence assessment and vaccine development.
Area of Science:
- Virology and Immunology
- Transgenic Animal Models
- Neuroscience
Background:
- Poliovirus infection causes poliomyelitis, a neurological disease.
- Assessing poliovirus neurovirulence is crucial for public health and vaccine development.
- Traditional methods often involve non-human primates, which are costly and ethically complex.
Purpose of the Study:
- To describe the utility of transgenic mice expressing the human poliovirus receptor (PVR) for studying poliovirus.
- To detail methods for analyzing poliovirus pathogenicity and host immune responses in this model.
- To highlight the advantages of the PVR-tg mouse model for research and surveillance.
Main Methods:
- Generation of transgenic (tg) mice expressing the human poliovirus receptor (CD155).
- Infection of PVR-tg mice with various poliovirus strains (wild-type, mutants, vaccine-derived).
- Assessment of neurovirulence, tissue tropism, and host immune responses in infected mice.
Main Results:
- PVR-tg mice are susceptible to poliovirus and develop poliomyelitis-like neurological disease.
- The model allows for the evaluation of neurovirulence for different poliovirus strains and mutants.
- PVR-tg mice are suitable for studying poliovirus tissue tropism and immune system interactions.
Conclusions:
- The PVR-tg mouse model provides a valuable, non-primate alternative for poliovirus research.
- This model is essential for assessing neurovirulence, surveillance of circulating polioviruses, and vaccine quality control.
- PVR-tg mice can be further utilized in combination with other genetically modified mouse lines for complex studies.
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