Host genetic diversity drives variable central nervous system lesion distribution in chronic phase of Theiler's Murine Encephalomyelitis Virus (TMEV) infection.
Host genetic diversity drives variable central nervous system lesion distribution in chronic phase of Theiler's Murine Encephalomyelitis Virus (TMEV) infection.
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DOI：
10.1371/journal.pone.0256370
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Brinkmeyer-Langford CL
中科院分区：
文献类型：
--
作者：
Lawley KS;Rech RR;Elenwa F;Han G;Perez Gomez AA;Amstalden K;Welsh CJ;Young CR;Threadgill DW;Brinkmeyer-Langford CL
宿主遗传背景是对病毒感染的神经反应变异性的重要驱动因素。在这里，我们利用遗传多样性的协作交叉（CC）小鼠资源来更好地了解泰勒氏小鼠脑脊髓炎病毒（TMEV）的慢性感染如何引起中枢神经系统（CNS）的多种临床和形态学变化。我们描述了tmev诱导的临床表型反应，以及6个CC小鼠品系在90天感染期内的相关中枢神经系统病变分布。我们在这些菌株中观察到不同程度的运动障碍，通过延迟翻正反射、麻痹、麻痹、癫痫发作、肢体紧握、皱褶和脑炎表型来测量。所有毒株均发生脑内神经实质坏死和矿化，主要发生在海马区。6株中2株表现为轴突变性伴腰椎神经根髓磷脂丢失。此外，我们将病变分布与临床表型和表型进展的总体频率进行统计关联，以更好地了解基于遗传背景的TMEV如何以及在何处靶向中枢神经系统。具体而言，我们评估了这些表型从早期到晚期TMEV疾病的病变分布与临床进展的关系，发现进展与病变分布之间存在显著关系。最后，我们确定了与特定脑区域病变频率相关的数量性状位点，揭示了未来研究的几个感兴趣的位点：溶酶体运输调节因子（Lyst）和nidogen 1 （Nid1）。总之，这些结果表明，遗传背景影响了临床表型的类型和严重程度，表型对TMEV的恢复能力以及菌株间的病变分布。
Host genetic background is a significant driver of the variability in neurological responses to viral infection. Here, we leverage the genetically diverse Collaborative Cross (CC) mouse resource to better understand how chronic infection by Theiler’s Murine Encephalomyelitis Virus (TMEV) elicits diverse clinical and morphologic changes in the central nervous system (CNS). We characterized the TMEV-induced clinical phenotype responses, and associated lesion distributions in the CNS, in six CC mouse strains over a 90 day infection period. We observed varying degrees of motor impairment in these strains, as measured by delayed righting reflex, paresis, paralysis, seizures, limb clasping, ruffling, and encephalitis phenotypes. All strains developed neuroparenchymal necrosis and mineralization in the brain, primarily localized to the hippocampal regions. Two of the six strains presented with axonal degeneration with myelin loss of the nerve roots in the lumbar spinal cord. Moreover, we statistically correlated lesion distribution with overall frequencies of clinical phenotypes and phenotype progression to better understand how and where TMEV targets the CNS, based on genetic background. Specifically, we assessed lesion distribution in relation to the clinical progression of these phenotypes from early to late TMEV disease, finding significant relationships between progression and lesion distribution. Finally, we identified quantitative trait loci associated with frequency of lesions in a particular brain region, revealing several loci of interest for future study: lysosomal trafficking regulator (Lyst) and nidogen 1 (Nid1). Together, these results indicate that the genetic background influences the type and severity of clinical phenotypes, phenotypic resilience to TMEV, and the lesion distribution across strains.
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DOI：
10.2353/ajpath.2007.060893
发表时间：
2007-02
期刊：
The American journal of pathology
影响因子：
--
作者：
Burrer R;Buchmeier MJ;Wolfe T;Ting JP;Feuer R;Iglesias A;von Herrath MG
通讯作者：
von Herrath MG
DOI：
10.1534/g3.118.200230
发表时间：
2018-07-31
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Konganti K;Ehrlich A;Rusyn I;Threadgill DW
通讯作者：
Threadgill DW
影响因子：
2.9
作者：
Bose, P;Fielding, R;Vacca-Galloway, LL
通讯作者：
Vacca-Galloway, LL
影响因子：
11.2
作者：
Cree, Bruce A. C.;Hollenbach, Jill A.;Hauser, Stephen L.
通讯作者：
Hauser, Stephen L.
影响因子：
6.4
作者：
Lassmann, Hans;Brueck, Wolfgang;Lucchinetti, Claudia F.
通讯作者：
Lucchinetti, Claudia F.