scholarly journals Viral Load and a Locus on Chromosome 11 Affect the Late Clinical Disease Caused by Theiler’s Virus

1999 ◽  
Vol 73 (10) ◽  
pp. 7965-7971 ◽  
Author(s):  
Stéphanie Aubagnac ◽  
Michel Brahic ◽  
Jean-François Bureau
Keyword(s):  
Multiple Sclerosis ◽  
Viral Load ◽  
Interferon Gamma ◽  
Persistent Infection ◽  
Demyelinating Disease ◽  
High Viral Load ◽  
Clinical Disease ◽  
Theiler's Virus ◽  
Chromosome 11 ◽  
Gamma Locus

ABSTRACT Theiler’s virus causes a persistent infection and a demyelinating disease of mice which is a model for multiple sclerosis. Susceptibility to viral persistence maps to several loci, including the interferon gamma locus. Inactivating the gene coding for the interferon gamma receptor makes 129/Sv mice susceptible to persistent infection and clinical disease, whereas inactivating the interferon gamma gene makes C57BL/6 mice susceptible to persistent infection but not to clinical disease. This difference in phenotype is due to the difference in genetic background. Clinical disease depends on high viral load andTmevd5, a locus on chromosome 11. These results have consequences for the identification of viruses which might be implicated in multiple sclerosis.

scholarly journals Theiler's virus infection of 129Sv mice that lack the interferon alpha/beta or interferon gamma receptors.

1995 ◽  
Vol 181 (6) ◽  
pp. 2069-2076 ◽  
Author(s):  
L Fiette ◽  
C Aubert ◽  
U Müller ◽  
S Huang ◽  
M Aguet ◽  
...  
Keyword(s):  
White Matter ◽  
Interferon Gamma ◽  
Interferon Alpha ◽  
Persistent Infection ◽  
Demyelinating Disease ◽  
Inbred Mice ◽  
Acute Infection ◽  
Theiler's Virus ◽  
Primary Demyelination ◽  
Alpha Beta

The Daniels strain of Theiler's virus causes a persistent infection of the white matter of spinal cord of susceptible mice, with chronic inflammation and primary demyelination. Inbred 129Sv mice are resistant to this infection; they present with mild encephalomyelitis and clear the infection within a matter of days. A very different outcome was observed with inbred 129Sv mice whose receptors for interferon alpha/beta or interferon gamma had been inactivated by homologous recombination. The former presented severe encephalomyelitis with acute infection of neurons, particularly in brain and hippocampus, and extensive infection with necrosis of the choroid plexus. Most animals died of this acute disease. The latter, presented the same early encephalomyelitis as the control 129Sv mice. However, they remained persistently infected and developed a very severe late infection of the white matter with extensive primary demyelination. This late disease looked like an exacerbated form of the chronic demyelinating disease observed in susceptible inbred mice such as the SJL/J or FVB strains. Our results show that the two interferon systems play nonredundant roles in the resistance of the 129Sv mouse to the infection by Theiler's virus. They also lend support to the notion that the Ifg gene is involved in the resistance/susceptibility of inbred strains of mice to persistent infection by this picornavirus.

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 microRNA-219 Reduces Viral Load and Pathologic Changes in Theiler's Virus-Induced Demyelinating Disease

2018 ◽  
Vol 26 (3) ◽  
pp. 730-743 ◽  
Author(s):  
Ana Lis Moyano ◽  
Jeffrey Steplowski ◽  
Haibo Wang ◽  
Kyung-No Son ◽  
Diana I. Rapolti ◽  
...  
Keyword(s):  
Viral Load ◽  
Demyelinating Disease ◽  
Theiler's Virus

scholarly journals Theiler's Virus Infection: a Model for Multiple Sclerosis

2004 ◽  
Vol 17 (1) ◽  
pp. 174-207 ◽  
Author(s):  
Emilia L. Oleszak ◽  
J. Robert Chang ◽  
Herman Friedman ◽  
Christos D. Katsetos ◽  
Chris D. Platsoucas
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Molecular Mimicry ◽  
Experimental Models ◽  
Demyelinating Diseases ◽  
Acute Disease ◽  
Theiler's Virus ◽  
Spinal Cord Atrophy ◽  
Demyelinating Lesions ◽  
Mononuclear Cell Infiltrates

SUMMARY Both genetic background and environmental factors, very probably viruses, appear to play a role in the etiology of multiple sclerosis (MS). Lessons from viral experimental models suggest that many different viruses may trigger inflammatory demyelinating diseases resembling MS. Theiler's virus, a picornavirus, induces in susceptible strains of mice early acute disease resembling encephalomyelitis followed by late chronic demyelinating disease, which is one of the best, if not the best, animal model for MS. During early acute disease the virus replicates in gray matter of the central nervous system but is eliminated to very low titers 2 weeks postinfection. Late chronic demyelinating disease becomes clinically apparent approximately 2 weeks later and is characterized by extensive demyelinating lesions and mononuclear cell infiltrates, progressive spinal cord atrophy, and axonal loss. Myelin damage is immunologically mediated, but it is not clear whether it is due to molecular mimicry or epitope spreading. Cytokines, nitric oxide/reactive nitrogen species, and costimulatory molecules are involved in the pathogenesis of both diseases. Close similarities between Theiler's virus-induced demyelinating disease in mice and MS in humans, include the following: major histocompatibility complex-dependent susceptibility; substantial similarities in neuropathology, including axonal damage and remyelination; and paucity of T-cell apoptosis in demyelinating disease. Both diseases are immunologically mediated. These common features emphasize the close similarities of Theiler's virus-induced demyelinating disease in mice and MS in humans.

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