Host genetic background influences diverse neurological responses to viral infection in mice.
Host genetic background influences diverse neurological responses to viral infection in mice.
复制标题
DOI：
10.1038/s41598-017-12477-2
复制
发表时间：
2017-09-22
影响因子：
4.6
通讯作者：
Threadgill DW
中科院分区：
文献类型：
--
作者：
Brinkmeyer-Langford CL;Rech R;Amstalden K;Kochan KJ;Hillhouse AE;Young C;Welsh CJ;Threadgill DW
Theiler鼠脑脊髓炎病毒（TMEV）感染是病毒感染引起的神经系统结果的模型，因为它会导致小鼠的不同神经系统疾病，这取决于感染的菌株。为了扩展对TMEV引起的异质性神经系统结局的认识，并确定与先前感染相关的人类神经系统疾病的新模型，我们分析了TMEV感染在协作交叉（CC）小鼠群体中的表型后果。我们使用神经和行为表型测试和组织学评估了5种不同CC菌株的长期感染（3个月）和急性与早期慢性感染（感染后7天与28天）的结果。我们将表型观察结果与先前与TMEV易感性相关的基因组区域的单倍型相关联，以检验CC小鼠内的基因组多样性导致对TMEV应答的可变疾病表型的假设。分析的5种菌株中没有一种具有与先前数据可用的任何其他CC菌株或近交系菌株相同的应答，表明CC菌株可以产生神经系统疾病的新模型。因此，CC菌株可以成为研究病毒感染如何根据宿主遗传背景导致不同神经学结果的强大资源。
Infection by Theiler’s murine encephalomyelitis virus (TMEV) is a model for neurological outcomes caused by virus infection because it leads to diverse neurological conditions in mice, depending on the strain infected. To extend knowledge on the heterogeneous neurological outcomes caused by TMEV and identify new models of human neurological diseases associated with antecedent infections, we analyzed the phenotypic consequences of TMEV infection in the Collaborative Cross (CC) mouse population. We evaluated 5 different CC strains for outcomes of long-term infection (3 months) and acute vs. early chronic infection (7 vs. 28 days post-infection), using neurological and behavioral phenotyping tests and histology. We correlated phenotypic observations with haplotypes of genomic regions previously linked to TMEV susceptibility to test the hypothesis that genomic diversity within CC mice results in variable disease phenotypes in response to TMEV. None of the 5 strains analyzed had a response identical to that of any other CC strain or inbred strain for which prior data are available, indicating that strains of the CC can produce novel models of neurological disease. Thus, CC strains can be a powerful resource for studying how viral infection can cause different neurological outcomes depending on host genetic background.
登录
查看更多内容
影响因子：
5.6
作者：
Berg, Anne T.;Berkovic, Samuel F.;Scheffer, Ingrid E.
通讯作者：
Scheffer, Ingrid E.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
6.7
作者：
ACHESON, ED
通讯作者：
ACHESON, ED
影响因子：
15.1
作者：
Campbell, T;Meagher, MW;Welsh, CJR
通讯作者：
Welsh, CJR
影响因子：
82.9
作者：
CHEN, HH;KONG, WP;ROOS, RP
通讯作者：
ROOS, RP