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Mapping loci influencing the persistence of Theiler's virus in the murine central nervous system
J F Bureau1, X Montagutelli, F Bihl
1Unité des Virus Lents, CNRS UA1157, Paris, France.
Abstract:
Inbred strains of mice differ greatly in their susceptibility to the demyelinating disease caused by Theiler's Murine Encephalomyelitis Virus. In this murine disease, which is an animal model for the study of multiple sclerosis, demyelination depends on the persistent infection of the central nervous system. Previous studies identified a locus in the H-2D region of the major histocompatibility complex which controls susceptibility to the persistent infection, and also showed that other loci are involved. In order to identify these loci, we screened the genome of a set of backcross animals with a combination of polymorphic microsatellites and restriction enzymes sites. We now show that viral persistence is also controlled by a locus close to Ifg on chromosome 10 and possibly by a locus near Mbp on chromosome 18.
Insights
Genetic factors influence susceptibility to Theiler
Area of Science:
- Neuroimmunology
- Virology
- Genetics
Background:
- Theiler's Murine Encephalomyelitis Virus (TMEV) infection in mice serves as a model for multiple sclerosis, characterized by central nervous system demyelination.
- Susceptibility to TMEV-induced demyelination is linked to persistent viral infection in the central nervous system.
- Previous research identified a susceptibility locus within the H-2D region of the major histocompatibility complex, but other genetic factors were implicated.
Purpose of the Study:
- To identify additional genetic loci controlling susceptibility to persistent Theiler's Murine Encephalomyelitis Virus infection.
- To further elucidate the genetic basis of TMEV-induced demyelination in a murine model.
Main Methods:
- Genome-wide screening of backcross mice using polymorphic microsatellites and restriction enzyme sites.
- Genetic mapping to identify loci associated with viral persistence.
Main Results:
- Viral persistence is controlled by a locus near Ifg on chromosome 10.
- A potential susceptibility locus was identified near Mbp on chromosome 18.
Conclusions:
- The genetic control of Theiler's Murine Encephalomyelitis Virus persistence involves multiple loci beyond the H-2D region.
- New genetic loci on chromosomes 10 and 18 contribute to susceptibility to viral persistence and demyelination in this multiple sclerosis model.