HLA-DQ Polymorphism Influences Progression of Demyelination and Neurologic Deficits in a Viral Model of Multiple Sclerosis

@article{Pavelko2000HLADQPI,
  title={HLA-DQ Polymorphism Influences Progression of Demyelination and Neurologic Deficits in a Viral Model of Multiple Sclerosis},
  author={Kevin D. Pavelko and Kristen M. Drescher and Dorian B. McGavern and Chella S. David and Moses Rodriguez},
  journal={Molecular and Cellular Neuroscience},
  year={2000},
  volume={15},
  pages={495-509}
}
The importance of genetic susceptibility in determining the progression of demyelination and neurologic deficits is a major focus in neuroscience. We studied the influence of human leukocyte antigen (HLA)-DQ polymorphisms on disease course and neurologic impairment in virus-induced demyelination. HLA-DQ6 or DQ8 was inserted as a transgene into mice lacking endogenous expression of MHC class I (beta(2)m) and class II (H2-A(beta)) molecules. Following Theiler's murine encephalomyelitis virus… 
Human HLA-DR Transgenes Protect Mice from Fatal Virus-Induced Encephalomyelitis and Chronic Demyelination
TLDR
The hypothesis that the expression of a single human class II MHC molecule can, by itself, influence the control of an intracerebral pathogen in a host without a competent class I MHC immune response is supported.
Human class I major histocompatibility complex alleles determine central nervous system injury versus repair
TLDR
The hypothesis that the expression of a single human class I MHC molecule, independent of persistent virus infection, influences the extent of sub frequent chronic neuronal injury or repair in the absence of a class II MHC immune response is supported.
Periventricular Demyelination and Axonal Pathology Is Associated with Subependymal Virus Spread in a Murine Model for Multiple Sclerosis
TLDR
The demonstration of ependymal infection and subjacent spread into the brain parenchyma as well as regional virus clearance despite ongoing demyelination and axonal damage in other CNS compartments allows new insights into TME pathogenesis.
Impact of Erb-B Signaling on Myelin Repair in the CNS Following Virus-Induced Damage
TLDR
Examination of a model of demyelination triggered by direct injection of Theiler s murine encephalomyelitis virus into the spinal cord suggests that animals that have been exogenously treated with glial growth factor have improved clinical function compared to animals receiving glia growth factor 2 or sensory motor derived factor.
Direct Comparison of Demyelinating Disease Induced by the Daniel's Strain and BeAn Strain of Theiler's Murine Encephalomyelitis Virus
TLDR
Findings indicate that the diseases induced by DA or BeAn are distinct, and functional deficits as measured by Rotarod were more severe in DA infected versus BeAn infected mice.
Untersuchung über die Virusausbreitung und -persistenz bei der murinen Theiler-Enzephalomyelitis von experimentell infizierten Mäusen mittels polyklonaler Antikörper und RNS-Sonden
TLDR
The aim of the study was to identify topographical differences of TMEV spread and demyelination in the CNS of experimentally infected susceptible SJL/J mice and resistant C57BL/6 mice.
Transgenic Expression of the 3D Polymerase Inhibits Theiler's Virus Infection and Demyelination
TLDR
It is found that 3D transgenic expression in genetically susceptible FVB mice led to substantially lower viral loads after infection with Theiler's murine encephalomyelitis virus (TMEV), which led to the preservation of large-diameter axons and motor function in these mice.
An Elite Controller of Picornavirus Infection Targets an Epitope That Is Resistant to Immune Escape
TLDR
The generated TMEV mutants that encode for mutations within the VP2121-130 peptide are generated, demonstrating that the virus is incapable of escaping the protective response and highlighting the importance of choosing appropriate vaccine antigens.
Immunogenetics, Resistance, and Susceptibility to Theiler’s Virus Infection
The genetic basis for differential susceptibility to Theiler’s virus-induced demyelinating disease is complex and often confusing, similar to the situation seen in analyzing the genetic risk for
Factors directly affecting impulse transmission in inflammatory demyelinating disease: recent advances in our understanding
TLDR
Demyelination and inflammation both contribute to the neurological deficits characteristic of multiple sclerosis and Guillain-Barré syndrome, and factors such as nitric oxide, endocaine, cytokines, and antiganglioside antibodies also play significant roles.

References

SHOWING 1-10 OF 43 REFERENCES
Expression of the human histocompatibility leukocyte antigen DR3 transgene reduces the severity of demyelination in a murine model of multiple sclerosis.
TLDR
These experiments are the first to demonstrate that a human class II DR gene can alter the severity of demyelination in an animal model of MS without influencing viral load.
Abrogation of resistance to Theiler's virus-induced demyelination in H-2b mice deficient in beta 2-microglobulin.
TLDR
The hypothesis that a class I immune response mediated by CD8+ T cells is important in resistance to Theiler's murine encephalomyelitis virus-induced demyelination is supported.
Perforin-Dependent Neurologic Injury in a Viral Model of Multiple Sclerosis
TLDR
Perforin-mediated cytotoxic effector function is necessary for viral clearance and may directly contribute to the development of neurologic deficits after demyelination in the Theiler’s murine encephalomyelitis virus (TMEV) model of multiple sclerosis.
Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis
TLDR
It is proposed that the mechanism by which demyelinated class I-deficient mice maintain neurologic function results from increased sodium channel densities and the relative preservation of axons and is the first to implicate a role for MHC class I in the development of neurological deficits following demYelination.
Theiler's virus persistence and demyelination in major histocompatibility complex class II-deficient mice
TLDR
It is demonstrated that class II gene products are required for virus clearance from the CNS but not for demyelination and neurologic disease.
Susceptibility to Theiler's virus-induced demyelination. Mapping of the gene within the H-2D region
TLDR
The findings in the congeneic recombinant mice and in mice mutant in the H-2D region strongly suggest that at least one of the genes critical for determining virus-induced demyelination maps to the 3' end of the H2D gene.
Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in mice is influenced by the H-2D region: correlation with TEMV-specific delayed-type hypersensitivity.
TLDR
Findings demonstrating a strong correlation between disease incidence, the presence of particular H-2D region genotypes, and high levels of TMEV-specific DTH in susceptible strains support the hypothesis that the disease is immune mediated rather than a result of direct cytolytic effects of virus infection.
Demyelination induced by Theiler's virus: influence of the H-2 haplotype.
TLDR
The observations support the hypothesis that susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination is influenced by genes that are linked to the H-2 complex and suggest that the demYelination may be mediated by immune cells rather than being a direct cytolytic effect of virus on oligodendrocytes.
The balance between persistent virus infection and immune cells determines demyelination.
TLDR
The hypothesis that demyelination is the result of a balance between persistent virus infection and immune injury mediated by either CD4+ or CD8+ T cells is supported.
...
1
2
3
4
5
...