Theiler's encephalomyelitis virus
Theiler's murine encephalomyelitis virus | |
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Virus classification | |
(unranked): | Virus |
Realm: | Riboviria |
Kingdom: | Orthornavirae |
Phylum: | Pisuviricota |
Class: | Pisoniviricetes |
Order: | Picornavirales |
Family: | Picornaviridae
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Genus: | Cardiovirus |
Species: | |
Virus: | Theiler's murine encephalomyelitis virus
|
Theiler's murine encephalomyelitis virus (TMEV) is a single-stranded
Discovery
The virus was discovered by
Strains
The several different strains of TMEV are characterized by their pathology as well as genetic sequencing and proteomics. The two major groups are listed below; there are several other strains in the same group as DA (such as BeAn).[citation needed]
GDVII
TMEV GDVII virus is characterized by acute encephalomyelitis in susceptible mice, with a high
DA
The TMEV DA strain, in contrast, is characterized by chronic encephalomyelitis in susceptible mice. Infection initiates in astrocytes and microglia, but persists in macrophages. This strain has been used as an acceptable model for human multiple sclerosis.[4] and epilepsy.[5][6][7][8] The DA strain has also been shown to inhibit IRF-3 phosphorylation, by inhibiting an unknown intermediate step after RIG-I/MDA5 activation of IKKε and TBK1 kinases. The L protein has been shown to be critical in this process, although the mechanism is unknown. The DA strain of TMEV also encodes for a L* protein that is likely involved in viral persistence in macrophages. This protein's influence on the murine immune system, therefore, could be beneficial in understanding immune-mediated demyelination in diseases such as multiple sclerosis.[9]
Analogies with multiple sclerosis/pathology
Multiple sclerosis is a chronic disease that results in demyelination of the axons in brain and spinal cord, which often leads to severe neurological problems and eventually paralysis. The symptoms of MS are largely immune mediated, but the mechanism of the immune system's initiation in this disease is unknown. It is likely that both genetic and environmental factors play a large role in the initiation and progression of the disease. There are a number of animal models for MS. A common one is known as Experimental autoimmune encephalomyelitis, while TMEV occurs via injection of TMEV, and is thus distinct from EAE.[citation needed]
One hypothesis for the initiation is that an infection stimulates the innate immune system, specifically perivascular microglia. This allows the entrance of T-cells, and microglia spread viral epitopes, along with myelin epitopes, to T cells, which then are activated to "attack" the myelin cells. This is the proposed course of disease in TMEV infection in mice.[10]
Many
The majority of mouse strains are not susceptible to the pathology associated with TMEV infection. As SJL/J mice are notoriously susceptible, the majority of studies exploring factors that could lead to MS utilize this strain.[12] Max Theiler also used the SJL/J strain to study the progression of a polio-like disease in mice.[citation needed]
References
- PMID 20610716.
- ^ "The Nobel Prize in Physiology or Medicine 1951".
- PMID 19870629.
- ^ ISBN 978-81-86846-73-5.
- PMID 21107134.
- S2CID 205688212.
- S2CID 28622085.
- S2CID 250041500.
- PMID 16911804.
- ^ Cara Mack et al. Microglia are activated to become competent antigen presenting and effector cells in the inflammatory environment of the Theiler's virus model of multiple sclerosis, Journal of Neuroimmunology, Volume 144, Issues 1–2, November 2003, Pages 68-79, doi: https://doi.org/10.1016/j.jneuroim.2003.08.032
- PMID 19412527.
- PMID 16824573.