Chromosome 14 Contains Determinants That Regulate Susceptibility to Theiler's Virus–Induced Demyelination in the Mouse

Genetics ◽  
1998 ◽  
Vol 148 (4) ◽  
pp. 1941-1949
Author(s):  
J-F Bureau ◽  
K M Drescher ◽  
L R Pease ◽  
T Vikoren ◽  
M Delcroix ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Major Histocompatibility Complex ◽  
Linkage Analysis ◽  
Demyelinating Disease ◽  
Theiler's Virus ◽  
Chromosome 14 ◽  
Virus Persistence ◽  
Histocompatibility Complex ◽  
Encephalomyelitis Virus ◽  
Two Peaks

Abstract Theiler's murine encephalomyelitis virus causes a chronic demyelinating disease in susceptible strains of mice that is similar to human multiple sclerosis. Several nonmajor histocompatibility complex–linked genes have been implicated as determinants of susceptibility or resistance to either demyelination or virus persistence. In this study, we used linkage analysis of major histocompatibility complex identical H-2d (DBA/2J × B10.D2) F2 intercross mice to identify loci associated with susceptibility to virus-induced demyelinating disease. In a 20-cM region on chromosome 14, we identified four markers, D14Mit54, D14Mit60, D14Mit61, and D14Mit90 that are significantly associated with demyelination. Because two peaks were identified, one near D14Mit54 and one near D14Mit90, it is possible that two loci in this region are involved in controlling demyelination.

scholarly journals Virus Persistence in an Animal Model of Multiple Sclerosis Requires Virion Attachment to Sialic Acid Coreceptors

2004 ◽  
Vol 78 (16) ◽  
pp. 8860-8867 ◽  
Author(s):  
A. S. Manoj Kumar ◽  
Honey V. Reddi ◽  
Aisha Y. Kung ◽  
Mauro Dal Canto ◽  
Howard L. Lipton
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Sialic Acid ◽  
Demyelinating Disease ◽  
Direct Role ◽  
Virus Persistence ◽  
Sialic Acid Binding ◽  
Relevant Animal Model ◽  
Encephalomyelitis Virus ◽  
The Central Nervous System

ABSTRACT Persistent Theiler's virus infection in the central nervous system (CNS) of mice provides a highly relevant animal model for multiple sclerosis. The low-neurovirulence DA strain uses sialic acid as a coreceptor for cell binding before establishing infection. During adaptation of DA virus to growth in sialic acid-deficient cells, three amino acid substitutions (G1100D, T1081I, and T3182A) in the capsid arose, and the virus no longer used sialic acid as a coreceptor. The adapted virus retained acute CNS virulence, but its persistence in the CNS, white matter inflammation, and demyelination were largely abrogated. Infection of murine macrophage but not oligodendrocyte cultures with the adapted virus was also significantly reduced. Substitution of G1100D in an infectious DA virus cDNA clone demonstrated a major role for this mutation in loss of sialic acid binding and CNS persistence. These data indicate a direct role for sialic acid binding in Theiler's murine encephalomyelitis virus persistence and chronic demyelinating disease.

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