A New Cell Model for Investigating Prion Strain Selection and Adaptation
A New Cell Model for Investigating Prion Strain Selection and Adaptation
复制标题
用于研究朊病毒株选择和适应的新细胞模型
DOI：
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
P. Klöhn
中科院分区：
文献类型：
--
作者：
Alexandra Philiastides;J. M. Ribes;Daniel Yip;Christian Schmidt;I. Benilova;P. Klöhn
朊病毒病是影响人类和动物的致命性神经退行性疾病。朊病毒株，错误折叠朊病毒蛋白的构象变体，与不同的临床和病理表型。宿主-菌株相互作用导致不同脑区的选择性损伤，并且它们负责菌株选择和/或适应，但潜在的分子机制尚不清楚。朊病毒株可以通过它们在体内和体外的细胞嗜性来区分，这表明对不同朊病毒株的易感性是由细胞因子决定的。神经母细胞瘤细胞系PK 1对朊病毒株Me 7不敏感，但对RML高度敏感。我们挑战了大量的克隆PK 1线与Me 7和成功地选择了高度Me 7敏感的亚克隆（PME），以调查是否可以扩大的朊病毒株库的PK 1。值得注意的是，与RML感染的PME克隆相比，Me 7感染的PME克隆更具蛋白酶抗性，这表明细胞适应的Me 7和RML是不同的朊病毒株。引人注目的是，Me 7-难治性细胞，包括PK 1和星形胶质细胞在皮质海马培养物中，是非常敏感的朊病毒，来自Me 7感染的PME细胞的匀浆，这表明Me 7在PME细胞中的通道导致扩展的宿主范围。因此，PME克隆代表了菌株选择和适应的引人注目的细胞模型。
Prion diseases are fatal neurodegenerative diseases that affect humans and animals. Prion strains, conformational variants of misfolded prion proteins, are associated with distinct clinical and pathological phenotypes. Host-strain interactions result in the selective damage of distinct brain areas and they are responsible for strain selection and/or adaptation, but the underlying molecular mechanisms are unknown. Prion strains can be distinguished by their cell tropism in vivo and in vitro, which suggests that susceptibility to distinct prion strains is determined by cellular factors. The neuroblastoma cell line PK1 is refractory to the prion strain Me7, but highly susceptible to RML. We challenged a large number of clonal PK1 lines with Me7 and successfully selected highly Me7-susceptible subclones (PME) to investigate whether the prion strain repertoire of PK1 can be expanded. Notably, the Me7-infected PME clones were more protease-resistant when compared to RML-infected PME clones, which suggested that cell-adapted Me7 and RML are distinct prion strains. Strikingly, Me7-refractory cells, including PK1 and astrocytes in cortico-hippocampal cultures, are highly susceptible to prions, being derived from homogenates of Me7-infected PME cells, suggesting that the passage of Me7 in PME cells leads to an extended host range. Thus, PME clones represent a compelling cell model for strain selection and adaptation.
影响因子：
5.6
作者：
Li, RL;Liu, T;Sy, MS
通讯作者：
Sy, MS
影响因子：
6.4
作者：
Vorberg, I;Raines, A;Priola, SA
通讯作者：
Priola, SA
证明受感染的 PC12 细胞中痒病菌株的多样性。
DOI：
10.1099/0022-1317-73-11-3027
发表时间：
1992
期刊：
The Journal of general virology
影响因子：
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作者：
Rubenstein,R;Deng,H;Race,RE;Ju,W;Scalici,CL;Papini,MC;Kascsak,RJ;Carp,RI
通讯作者：
Carp,RI