Characterization of Plaque-Sized Variants of Daniel’s (DA) Strain in Theiler’s Virus-Induced Epilepsy

Epilepsy is a complex neurological disease characterized by recurrent seizures. Patients with viral encephalitis have a 16-fold increased risk of developing epilepsy, and this risk can persist for about 15 years after the occurrence of initial viral infection. Theiler’s murine encephalomyelitis viru...

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Bibliographic Details
Published in:	Scientific reports Vol. 9; no. 1; p. 3444
Main Authors:	Bijalwan, M., Young, C. R., Tingling, J., Zhou, X. J., Rimmelin, A. R., Leibowitz, J. L., Welsh, C. J.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 05-03-2019 Nature Publishing Group
Subjects:	13/1 13/31 13/51 631/250/371 631/378/1689/178 Convulsions & seizures Encephalitis Encephalomyelitis Epilepsy Genomes Humanities and Social Sciences Immune response Inflammation multidisciplinary Neurological diseases Nucleotide sequence Phenotypes Rodents Science Science (multidisciplinary) Seizures Viral infections
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Summary:	Epilepsy is a complex neurological disease characterized by recurrent seizures. Patients with viral encephalitis have a 16-fold increased risk of developing epilepsy, and this risk can persist for about 15 years after the occurrence of initial viral infection. Theiler’s murine encephalomyelitis virus (TMEV) infection induces a well-characterized experimental model of epilepsy in C57BL/6 mice. In response to intracerebral (I.C.) injection of Daniel’s (DA) strain of TMEV, there is vigorous immune response, which is detrimental to neurons and contributes to acute seizures, rendering mice susceptible to epilepsy. A comparative in vivo challenge study with either one of the two variants of the DA strain, small (DA-D S ) or large (DA-C L ) plaque forming variants, revealed differences in the diseases they induced in C57BL/6 mice. Compared to DA-C L -, DA-D S -infected mice exhibited significantly more seizures, higher clinical scores, neuroinflammation, and neuronal damage (mainly in the CA1-CA2 regions of hippocampus). Moreover, the brains of DA-D S infected mice contained approximately five-fold higher virus than those of DA-C L infected mice. A sequence comparison of the DA-C L and DA-D S genome sequences showed mutations in the leader (L) and L* proteins of DA-C L variant, which may be the cause of attenuating phenotype of DA-C L variant in the C57BL/6 mouse model of epilepsy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-019-38967-z