Characterization of Plaque-Sized Variants of Daniel's (DA) Strain in Theiler's Virus-Induced Epilepsy
Characterization of Plaque-Sized Variants of Daniel's (DA) Strain in Theiler's Virus-Induced Epilepsy
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DOI：
10.1038/s41598-019-38967-z
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发表时间：
2019-03-05
影响因子：
4.6
通讯作者：
Welsh, C. J.
中科院分区：
文献类型：
--
作者：
Bijalwan, M.;Young, C. R.;Welsh, C. J.
癫痫是一种以反复发作为特征的复杂神经系统疾病。病毒性脑炎患者发生癫痫的风险增加16倍，这种风险在最初病毒感染发生后可持续约15年。泰勒氏小鼠脑脊髓炎病毒（TMEV）感染诱导C57BL/6小鼠癫痫的实验模型。脑内注射Daniel’s （DA）株TMEV后，小鼠产生强烈的免疫反应，对神经元有害，导致急性癫痫发作，使小鼠易患癫痫。一项对DA菌株的两种变体，小（DA- d - s）或大（DA- c - l）斑块形成变体中的任何一种进行的体内比较攻击研究，揭示了它们在C57BL/6小鼠中诱导的疾病的差异。与DA-C-L-相比，da - d - s感染小鼠表现出明显更多的癫痫发作、更高的临床评分、神经炎症和神经元损伤（主要在海马CA1-CA2区）。此外，DA-D-S感染小鼠大脑中的病毒含量比DA-C-L感染小鼠高约5倍。对DA-C-L和DA-D-S基因组序列进行序列比较，发现DA-C-L变异的先导蛋白(L)和L*蛋白发生突变，这可能是导致DA-C-L变异在C57BL/6癫痫小鼠模型中表型减弱的原因。
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.