朊病毒通过肠道扩散到大脑？怎么做到的？

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导读：近日，来自爱丁堡大学的研究人员通过研究揭示了感染性蛋白如何引发疾病扩散到大脑，这或可帮助对致死性大脑疾病的患者进行诊断，相关研究发表于国际杂志Journal of Virology上。文章中研究者表示，个体在食用被感染性蛋白—朊病毒污染的食物后，朊病毒就会通过肠道侵入到个体大脑，该研究或将帮助对朊病毒疾病的诊断，朊病毒疾病包括克雅二氏症及疯牛病等。

早在20年前这种疾病非常罕见，当时229名患者死于克雅二氏症，朊病毒是一种具有异常形状的感染性蛋白，其可以通过食用污染的肉类在人群和动物之间传播，截止到目前为止研究者尚不清楚朊病毒通过肠道侵袭到大脑中的分子机制。

这项研究中研究者就朊病毒如何在小鼠机体中通过肠道入侵到大脑中进行了详尽的研究，研究者发现，朊病毒在扩散到大脑之前必须在小肠内壁建立自身特殊的结构，而肠道内壁一种名为淋巴集结的特殊结构是机体的部分免疫系统，而且可以形成机体对于污染食物的第一道防线，朊病毒就会拦截淋巴集结来引发感染。




在后期感染阶段朊病毒并不会在大肠内壁建立类似于补丁样的斑块结构，在此阶段朊病毒可以在淋巴结和脾脏中被检测到。据最新估计在英国大约有2000感染朊病毒的患者，但这些患者并没有表现出任何症状，在常规的阑尾切除手术中研究者对来自其机体的组织进行了分析。

研究者表示，我们的估测或许并不能鉴别出处于早期感染阶段的患者，而处于早期阶段朊病毒并不会越过小肠进行感染；当朊病毒进入大脑后，其就会破坏神经细胞引发一系列神经病变，比如记忆缺失、人格改变甚至移动困难。

最后研究者Neil Mabbott说道，是否所有个体通过肠道朊病毒感染继而发展为神经系统疾病我们不得而知，后期我们还需要进行更多的研究来寻找是什么因子可以增强机体对朊病毒的一感染，这对于研究朊病毒的致病机制及开发保护性措施或疗法来抑制朊病毒疾病提供了新的思路和希望。

ABSTRACT

Prion diseases are infectious neurodegenerative disorders characterised by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally and following exposure the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsies has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk to infection and the pre-clinical diagnosis of disease.

原文链接：
http://jvi.asm.org/content/early/2015/07/03/JVI.01544-15
doi:10.1128/JVI.01544-15