Neurobiology Division; The Roslin Institute and R(D)SVS; University of Edinburgh; Easter Bush, Scotland UK.
Prion. 2013 Jul-Aug;7(4):272-5. doi: 10.4161/pri.25420. Epub 2013 Jun 18.
Central to understanding the nature TSE agents (or prions) is how their genetic information is distinguished from the host. Are TSEs truly infectious diseases with host-independent genomes, or are they aberrations of a host component derived from the host genome? Recent experiments tested whether glycosylation of host PrP affects TSE strain characteristics. Wild-type mice were infected with 3 TSE strains passaged through transgenic mice with PrP devoid of glycans at 1 or both N-glycosylation sites. Strain-specific characteristics of 1 TSE strain changed but did not change for 2 others. Changes resulted from the selection of mutant TSE strains in a novel replicative environment. In general the properties of established TSEs support the genetic independence of TSE agents from the host, and specifically the primary structure of PrP does not directly encode TSE agent properties. However sporadic TSEs, challenge this independency. The prion hypothesis explains emerging TSEs relatively successfully but poorly accounts for the diversity and mutability of established TSE strains, or how many different infectious conformations are sustained thermodynamically. Research on early changes in RNA expression and events at the ribosome may inform the debate on TSE agent properties and their interaction with host cell machinery.
理解朊病毒（或朊粒）性质的核心问题是，它们的遗传信息如何与宿主区分开来。朊病毒病是真正具有独立于宿主的基因组的传染性疾病，还是宿主源自宿主基因组的一种异常成分？最近的实验检验了宿主 PrP 的糖基化是否影响朊病毒株的特征。野生型小鼠感染了 3 种通过转染缺乏 1 个或 2 个 N-糖基化位点糖基的 PrP 的转基因小鼠传代的朊病毒株。1 种朊病毒株的株特征发生了变化，但另外 2 种没有变化。这些变化是由于在新的复制环境中选择了突变的朊病毒株所致。总的来说，已建立的朊病毒的特性支持朊病毒剂与宿主的遗传独立性，并且 PrP 的一级结构不直接编码朊病毒剂的特性。然而，散发性朊病毒病对这种独立性提出了挑战。朊病毒假说相对成功地解释了新出现的朊病毒病，但朊病毒株的多样性和可变性，或者有多少种不同的感染构象在热力学上得以维持，解释得并不完善。关于 RNA 表达早期变化和核糖体上事件的研究可能会为朊病毒剂特性及其与宿主细胞机制的相互作用的争论提供信息。
