Enhancement of blood-brain barrier permeability is required for intravenously administered virus neutralizing antibodies to clear an established rabies virus infection from the brain and prevent the development of rabies in mice.
Enhancement of blood-brain barrier permeability is required for intravenously administered virus neutralizing antibodies to clear an established rabies virus infection from the brain and prevent the development of rabies in mice.
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DOI：
10.1016/j.antiviral.2014.07.013
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发表时间：
2014-10
影响因子：
7.6
通讯作者：
Fu, Zhen F.
中科院分区：
文献类型：
--
作者：
Huang, Chien-Tsun;Li, Zhenguang;Huang, Ying;Zhang, Guoqing;Zhou, Ming;Chai, Qingqing;Wu, Hua;Fu, Zhen F.
当血脑屏障通透性增加时，静脉注射VNAs可保护小鼠免于发生狂犬病。MCP-1通过下调脑微血管中的TJ蛋白来增强BBB通透性。BBB通透性的增强与CNS中VNA的增加和RABV从CNS的清除相关。狂犬病病毒（RABV）是一种嗜神经病毒，在人类和动物中引起致命疾病。目前，一旦出现临床症状，狂犬病就无法治愈。据信，一旦RABV进入中枢神经系统（CNS），外周中的病毒中和抗体（VNA）就不能穿过血脑屏障（BBB）并进入CNS。此外，已经假设在CNS中通过侵入B细胞产生的VNA，而不是在外周产生然后转运到CNS中的VNA，在从CNS清除RABV中是重要的。在本研究中，将含有VNA的小鼠血清静脉内给予野生型RABV感染后的小鼠。我们的研究表明，外源性VNA的管理是至关重要的RABV从大脑中的清除，并防止狂犬病的发展，在免疫功能正常和免疫功能低下的小鼠，只要BBB通透性保持增强。因此，本研究为开发VNA治疗人类临床狂犬病的可能性提供了基础。
Intravenous administration of VNAs can protect mice from developing rabies when the BBB permeability is enhanced. MCP-1 enhances BBB permeability by down-regulation of TJ proteins in the brain microvasculature. Enhancement of the BBB permeability correlates with the increase of VNA in and the clearance of RABV from the CNS. Rabies virus (RABV) is a neurotropic virus that causes fatal disease in humans and animals. Currently there is no cure for rabies once clinical signs appear. It is believed that once RABV enters the central nervous system (CNS), virus neutralizing antibodies (VNAs) in the periphery cannot pass through the blood–brain barrier (BBB) and into the CNS. Furthermore, it has been hypothesized that VNAs produced in the CNS by invading B cells, rather than those produced in the periphery and then transported into the CNS, are important in clearing RABV from the CNS. In the present study, mouse serum containing VNA was administered intravenously into mice after infection with wild-type RABV. Our studies demonstrate that exogenous administration of VNAs is crucial in the clearance of RABV from the brain and prevent the development of rabies in both immunocompetent and immunocompromised mice as long as the BBB permeability remains enhanced. This present study therefore provides a foundation for the possibility of developing VNA therapy for clinical rabies in humans.
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影响因子：
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