Department of Veterinary Medicine, University of Alaska Fairbanks, Fairbanks, Alaska, United States of America.
Department of Pharmaceutical Sciences, University of the Sciences, Philadelphia, Pennsylvania, United States of America.
Sci Rep. 2017 Oct 9;7(1):12818. doi: 10.1038/s41598-017-12726-4.
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.
狂犬病病毒会导致感染宿主的行为发生剧烈变化。但目前尚不清楚用于实现这些宿主变化的机制。本研究的主要发现是，狂犬病病毒糖蛋白中的一个区域与蛇毒素具有同源性，它能够通过抑制中枢神经系统中存在的烟碱型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以及一般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了α4β2 烟碱型乙酰胆碱受体的反应，全长狂犬病病毒糖蛋白的外域也是如此。相同的肽在秀丽隐杆线虫中显著改变了烟碱型受体诱导的行为，并在注射到小鼠中枢神经系统时增加了运动活动水平。这些结果为感染狂犬病病毒的宿主的行为变化提供了一种机制解释。
