Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS.
Rabies virus modifies host behaviour through a snake-toxin like region of its glycoprotein that inhibits neurotransmitter receptors in the CNS.
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DOI：
10.1038/s41598-017-12726-4
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发表时间：
2017-10-09
影响因子：
4.6
通讯作者：
Schulte MK
中科院分区：
文献类型：
--
作者：
Hueffer K;Khatri S;Rideout S;Harris MB;Papke RL;Stokes C;Schulte MK
狂犬病病毒在受感染的宿主中引起剧烈的行为改变。用于在宿主中实现这些改变的机制尚不清楚。这项研究的主要发现是，狂犬病病毒糖蛋白中的一个区域与蛇毒素具有同源性，能够通过抑制中枢神经系统中的烟碱乙酰胆碱受体来改变动物的行为。这一发现为病毒受体相互作用和病原体对宿主的操纵提供了一个新的方面。狂犬病病毒糖蛋白的神经毒素样区域在体外抑制α4β2烟碱受体的乙酰胆碱反应，狂犬病病毒糖蛋白的全长胞外域也是如此。相同的肽显著改变了C. elegans和增加的自发活动水平时，注射到小鼠的中枢神经系统。这些结果为狂犬病病毒感染宿主的行为变化提供了一种机制性解释。
Rabies virus induces drastic behaviour modifications in infected hosts. The mechanisms used to achieve these changes in the host are not known. The main finding of this study is that a region in the rabies virus glycoprotein, with homologies to snake toxins, has the ability to alter behaviour in animals through inhibition of nicotinic acetylcholine receptors present in the central nervous system. This finding provides a novel aspect to virus receptor interaction and host manipulation by pathogens in general. The neurotoxin-like region of the rabies virus glycoprotein inhibited acetylcholine responses of α4β2 nicotinic receptors in vitro, as did full length ectodomain of the rabies virus glycoprotein. The same peptides significantly altered a nicotinic receptor induced behaviour in C. elegans and increased locomotor activity levels when injected into the central nervous system of mice. These results provide a mechanistic explanation for the behavioural changes in hosts infected by rabies virus.
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