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A Model for Epilepsy of Infectious Etiology using Theiler's Murine Encephalomyelitis Virus
Published on: June 23, 2022
ENCEPHALOMYELITIS OF MICE : I. CHARACTERISTICS AND PATHOGENESIS OF THE VIRUS
1Laboratories of the International Health Division of The Rockefeller Foundation, New York.
Abstract:
1. The two strains of virus named GD VII and FA, respectively, accidentally discovered during experiments with yellow fever, have been shown to be immunologically related to each other, as well as to the virus of mouse encephalomyelitis. 2. Infection of the central nervous system can be produced with both strains by intracerebral, intranasal, or intraperitoneal inoculations. The cardinal symptom produced by the GD VII strain of virus by all three methods of inoculation is a flaccid paralysis of the limbs. The symptoms produced by the FA strain are referable to lesions of the brain when infection is produced by intracerebral and intranasal inoculation. Following intraperitoneal inoculation of the FA strain of virus, however, a flaccid paralysis is usually produced. 3. By the use of graded collodion membranes the particle size of the virus of mouse encephalomyelitis has been shown to be from 9 to 13 mmicro 4. The stability of the virus at different hydrogen ion concentrations has been tested. It has been found that there are two optima of stability, one at about pH 8.0 and the other at pH 3.3. 5. The virus is readily inactivated at 37 degrees C. by 1 per cent hydrogen peroxide. 6. Of organic solvents tested, ether had no action, whereas ethyl alcohol in 20 per cent concentration almost completely inactivated the virus after 45 minutes in the cold. 7. The virus can be precipitated by means of ammonium sulfate. 8. With increasing age mice acquire a relative resistance to the virus. 9. Immunity to a subsequent intracerebral inoculation can be produced by intraperitoneal, as well as intranasal, administrations of relatively large amounts of virus. 10. Mice infected by the intracerebral inoculation of a relatively avirulent virus acquire a high degree of immunity to a subsequent inoculation of a highly virulent strain. 11. The course of infection in mice following intracerebral, intranasal, and intraperitoneal inoculation of the FA strain of virus has been studied.
Insights
Two virus strains, GD VII and FA, are immunologically related to mouse encephalomyelitis virus. These viruses cause central nervous system infections in mice, with GD VII inducing paralysis and FA causing brain lesions or paralysis depending on inoculation route.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Two novel virus strains, GD VII and FA, were identified during yellow fever research.
- These strains exhibit immunological relatedness to each other and to the mouse encephalomyelitis virus.
Purpose of the Study:
- To characterize the GD VII and FA virus strains.
- To investigate their infectivity, pathogenic effects, and physical/chemical properties.
- To explore potential for inducing immunity in a mouse model.
Main Methods:
- Inoculation of mice via intracerebral, intranasal, and intraperitoneal routes.
- Particle size determination using graded collodion membranes.
- Assessment of virus stability across a range of pH values and susceptibility to chemical agents (hydrogen peroxide, ethyl alcohol).
- Evaluation of inactivation by organic solvents and precipitation by ammonium sulfate.
- Investigation of age-related resistance and induced immunity through different inoculation methods.
Main Results:
- Both GD VII and FA viruses can infect the central nervous system in mice.
- GD VII primarily causes flaccid paralysis; FA causes brain lesions or paralysis depending on the inoculation route.
- Mouse encephalomyelitis virus particle size ranges from 9 to 13 mmicro.
- Optimal virus stability observed at pH 8.0 and pH 3.3.
- Virus is inactivated by 1% hydrogen peroxide at 37°C and 20% ethyl alcohol.
- Ammonium sulfate precipitates the virus.
- Older mice show increased resistance.
- Intraperitoneal and intranasal inoculation can induce immunity.
- Infection with an avirulent strain confers immunity to a virulent strain.
Conclusions:
- GD VII and FA viruses represent significant agents capable of causing neurological disease in mice.
- Understanding their physical, chemical, and immunological properties is crucial for developing countermeasures.
- Age and prior infection influence host susceptibility and immunity, offering insights into disease prevention strategies.
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