BIOLOGICAL EVIDENCE THAT SCRAPIE AGENT HAS AN INDEPENDENT GENOME
BIOLOGICAL EVIDENCE THAT SCRAPIE AGENT HAS AN INDEPENDENT GENOME
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DOI：
10.1099/0022-1317-68-1-79
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发表时间：
1987-01-01
影响因子：
3.8
通讯作者：
DICKINSON, AG
中科院分区：
文献类型：
--
作者：
BRUCE, ME;DICKINSON, AG
有许多不同的羊瘙痒病病原体菌株，通过它们在特定基因型的近交系小鼠中的相对潜伏期和定量和定性神经病理学特性来鉴定。当在小鼠品系、感染途径和感染剂量的特定条件下连续传代时，这些特性是稳定的。然而，如果通道策略改变，它们可能以可预测的方式改变。羊瘙痒病菌株87 A显示了先前定义的III类稳定性;在C57 BL小鼠中以低剂量传代时稳定，但如果使用高剂量，则通常在单次传代过程中突然改变其特性，总是产生相同的新菌株。后者命名为7 D，与87 A相比，具有更短的潜伏期和更广泛的病理学，即使在高剂量下，这些性质随后在连续传代中也是稳定的。这种现象已被反复使用羊瘙痒症分离株从六个不同的自然情况下，在五个不同品种的羊。这些分离株在所有性质上都非常相似，表明它们是87 A菌株的独立分离株;没有任何87 A菌株的分离株不发生这种现象。另一方面，在同一实验室中使用的许多其他羊瘙痒病菌株都没有显示出这种变化。87 A大脑样本的行为一直表现得好像它们含有87 A和少量的7 D。即使在87 A之前已经在高稀释度下传代，远远超过7 D的有限稀释度，这也是如此，该程序将消除分离物中最初存在的任何次要因子菌株。因此，感染87 A的小鼠组织中的7 D极有可能是在孵育期间通过87 A的突变变化在每次传代时从头产生的。许多不同的菌株存在的既定事实和突变可能发生的大量证据导致得出这样的结论，即羊瘙痒病病原体有自己独立复制的基因组。
There are many distinct strains of scrapie agent, identified by their relative incubation periods and quantitative and qualitative neuropathological properties in inbred mice of particular genotypes. When serially passaged under specified conditions of mouse strain, route of infection and dose of infectivity these properties are stable. However, they may change in a predictable manner if the passage strategy is altered. The scrapie strain 87A shows what has previously been defined as Class III stability; it is stable when passaged at low dose in C57BL mice, but often suddenly changes its properties in the course of a single passage if high doses are used, always resulting in the same new strain. The latter, designated 7D, has shorter incubation periods and more extensive pathology than 87A, properties which are subsequently stable on serial passage even at high dose. This phenomenon has been seen repeatedly using scrapie isolates from six different natural cases in five different breeds of sheep. These isolates are closely similar in all their properties, showing them to be independent isolations of the 87A strain; there have been no isolations of 87A in which the phenomenon did not occur. On the other hand, none of the many other scrapie strains used in the same laboratory have shown this change. 87A brain samples consistently behave as if they contain 87A together with a smaller amount of 7D. This is so even after 87A has previously been passaged at high dilution, well beyond the limiting dilution for 7D, a procedure which would eliminate any minor agent strain originally present in the isolate. Therefore it is highly likely that the 7D in tissues of mice infected with 87A is generated de novo at each passage by mutational change from 87A during the incubation period. The established fact that many different strains exist and the considerable evidence that mutation can occur lead to the conclusion that scrapie agent has its own independently replicating genome.