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热对传染性海绵状脑病剂株影响的特性描述。

Characterization of the effect of heat on agent strains of the transmissible spongiform encephalopathies.

机构信息

Neuropathogenesis Division, The Roslin Institute and Royal (Dick) Veterinary School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, EH25 9PS, Scotland, UK.

出版信息

J Gen Virol. 2011 Jul;92(Pt 7):1738-1748. doi: 10.1099/vir.0.030452-0. Epub 2011 Apr 6.

DOI:10.1099/vir.0.030452-0
PMID:21471321
Abstract

The causal agents of the transmissible spongiform encephalopathy (TSE) diseases, sometimes called prion diseases, are characterized by high resistance to inactivation with heat. Results from thermal inactivation experiments on nine TSE strains, seven passaged in two PrP genotypes, showed differences in sensitivity to heat inactivation ranging over 17 °C. In addition, the rate of inactivation with increasing temperature varied between TSE models. In some cases passage in an alternative PrP genotype had little effect on the resulting inactivation properties, but for others the infectious agent was inactivated at lower temperatures. No strain with higher thermostability properties was selected. The effect of mixing two TSE strains, to see whether their properties were affected through interaction with each other, was also examined. The results showed that both strains behaved as expected from the behaviour of the unmixed controls, and that the strain responsible for inducing TSE disease could be identified. There was no evidence of a direct effect on intrinsic strain properties. Overall, the results illustrate the diversity in properties of TSE strains. They require intrinsic molecular properties of TSE agents to accommodate high resistance to inactivation and a mechanism, independent of the host, to directly encode these differences. These findings are more readily reconciled with models of TSE agents with two separate components, one of which is independent of the host and comprises a TSE-specific nucleic acid, than with models based solely on conformational changes to a host protein.

摘要

传染性海绵状脑病(TSE)疾病的病原体,有时也称为朊病毒疾病,其特点是对热失活具有很高的抗性。对 9 种 TSE 株进行热失活实验的结果表明,对热失活的敏感性差异超过 17°C。此外,TSE 模型之间的失活速率随温度升高而变化。在某些情况下,在替代 PrP 基因型中传代对产生的失活特性几乎没有影响,但对于其他 TSE 株,感染因子在较低温度下失活。没有选择耐热性更高的菌株。还检查了混合两种 TSE 株以观察它们是否通过相互作用而影响其特性的效果。结果表明,两种菌株的行为均与未混合对照的行为相符,可以识别出引起 TSE 疾病的菌株。没有证据表明存在对固有株特性的直接影响。总体而言,这些结果说明了 TSE 株特性的多样性。它们需要 TSE 剂的固有分子特性来适应高抗失活性,并且需要一种独立于宿主的机制来直接编码这些差异。这些发现与具有两个独立成分的 TSE 剂模型更相符,其中一个成分独立于宿主,并且包含 TSE 特异性核酸,而与仅基于宿主蛋白构象变化的模型更不相符。

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