Department of Infectology, Scripps Florida, 130 Scripps Way, Jupiter, Florida 33458, USA.
EMBO Rep. 2011 Dec 1;12(12):1243-50. doi: 10.1038/embor.2011.191.
Murine prions transferred from brain to cultured cells gradually adapt to the new environment. Brain-derived 22L prions can infect neuroblastoma-derived PK1 cells in the presence of swainsonine (swa); that is, they are 'swa resistant'. PK1 cell-adapted 22L prions are swa sensitive; however, propagation in swa results in selection of swa-resistant substrains. Cloned, PK1 cell-adapted 22L prions were initially unable to develop swa resistance ('swa incompetent'); however, after serial propagation for 30-90 doublings, four of nine clones became swa competent, showing that swa-resistant 'mutants' arose during replication. Mutations in the case of prions are attributed to heritable changes in PrP(Sc) conformation. One clone remained swa incompetent even after 10(35)-fold expansion; surprisingly, after propagation in brain, it yielded swa-resistant prions, indistinguishable from the original 22L population. Thus, cell-adapted 22L prions assumed either mutable or virtually immutable conformations; however, when passaged through the brain all became mutable. Mutability is thus a substrain-specific attribute.
从大脑转移到培养细胞中的鼠朊病毒逐渐适应新环境。在 swainsonine (swa) 的存在下，源自大脑的 22L 朊病毒可以感染源自神经母细胞瘤的 PK1 细胞；也就是说，它们是“swa 抗性”的。适应 PK1 细胞的 22L 朊病毒对 swa 敏感；然而，在 swa 中的繁殖导致 swa 抗性亚株的选择。克隆的、适应 PK1 细胞的 22L 朊病毒最初无法产生 swa 抗性（“swa 不适应”）；然而，在 30-90 次倍增的连续繁殖后，9 个克隆中的 4 个变得 swa 适应，表明在复制过程中出现了 swa 抗性“突变体”。朊病毒的突变归因于 PrP(Sc)构象的可遗传变化。一个克隆即使在 10(35)倍的扩展后仍然 swa 不适应；令人惊讶的是，在大脑中繁殖后，它产生了与原始 22L 群体无法区分的 swa 抗性朊病毒。因此，适应细胞的 22L 朊病毒具有可变性或几乎不可变的构象；然而，当通过大脑传递时，所有的朊病毒都变得可变性。可变性因此是亚株特异性的属性。
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