Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions.
Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions.
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DOI：
10.3390/ijms222111379
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发表时间：
2021-10-21
影响因子：
5.6
通讯作者：
Threadgill DW
中科院分区：
文献类型：
--
作者：
Brinkmeyer-Langford C;Amstalden K;Konganti K;Hillhouse A;Lawley K;Perez-Gomez A;Young CR;Welsh CJ;Threadgill DW
由泰勒氏鼠脑脊髓炎病毒（TMEV）感染引起的病毒诱导的神经系统后遗症用于研究从癫痫发作到脱髓鞘疾病的人类疾病。基于病毒持久性和极端表型，如脱髓鞘，通常认为小鼠品系对TMEV感染易感或耐药。我们通过感染遗传多样性协作杂交（CC）小鼠资源的品系，确定了更广泛的表型结果。我们评估了慢性感染的基因表达谱的campi和胸脊髓的19 CC株的表型严重程度和TMEV的持久性。菌株聚类相似的表型配置文件和TMEV水平在感染后90天，我们分类不同的TMEV响应配置文件。三种最常见的特征包括“耐药”和“易感”，如前所述，以及“弹性”TMEV反应组，其即使在感染后90天也经历了TMEV持续性和轻度神经学表型。每个图谱都有不同的基因表达特征，可以识别每个TMEV反应组的特异性途径和网络。参与这些途径/网络的基因的CC创始人单倍型揭示了候选应答特异性等位基因。这些等位基因在长期TMEV感染中表现出多效性和表观遗传（miRNA）调控，与弹性小鼠品系特别相关。
Virus-induced neurological sequelae resulting from infection by Theiler’s murine encephalomyelitis virus (TMEV) are used for studying human conditions ranging from epileptic seizures to demyelinating disease. Mouse strains are typically considered susceptible or resistant to TMEV infection based on viral persistence and extreme phenotypes, such as demyelination. We have identified a broader spectrum of phenotypic outcomes by infecting strains of the genetically diverse Collaborative Cross (CC) mouse resource. We evaluated the chronic-infection gene expression profiles of hippocampi and thoracic spinal cords for 19 CC strains in relation to phenotypic severity and TMEV persistence. Strains were clustered based on similar phenotypic profiles and TMEV levels at 90 days post-infection, and we categorized distinct TMEV response profiles. The three most common profiles included “resistant” and “susceptible,” as before, as well as a “resilient” TMEV response group which experienced both TMEV persistence and mild neurological phenotypes even at 90 days post-infection. Each profile had a distinct gene expression signature, allowing the identification of pathways and networks specific to each TMEV response group. CC founder haplotypes for genes involved in these pathways/networks revealed candidate response-specific alleles. These alleles demonstrated pleiotropy and epigenetic (miRNA) regulation in long-term TMEV infection, with particular relevance for resilient mouse strains.
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影响因子：
7.3
作者：
Borba VV;Zandman-Goddard G;Shoenfeld Y
通讯作者：
Shoenfeld Y
影响因子：
14.9
作者：
Blake JA;Baldarelli R;Kadin JA;Richardson JE;Smith CL;Bult CJ;Mouse Genome Database Group
通讯作者：
Mouse Genome Database Group
影响因子：
3.7
作者：
Cammaerts S;Strazisar M;De Rijk P;Del Favero J
通讯作者：
Del Favero J
影响因子：
5.6
作者：
Afrasiabi A;Fewings NL;Schibeci SD;Keane JT;Booth DR;Parnell GP;Swaminathan S
通讯作者：
Swaminathan S
影响因子：
3.3
作者：
Chatel-Chaix, Laurent;Boulay, Karine;Mouland, Andrew J.;DesGroseillers, Luc
通讯作者：
DesGroseillers, Luc