Lethal silver-haired bat rabies virus infection can be prevented by opening the blood-brain barrier
Lethal silver-haired bat rabies virus infection can be prevented by opening the blood-brain barrier
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DOI：
10.1128/jvi.00710-07
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发表时间：
2007-08-01
影响因子：
5.4
通讯作者：
Hooper, D. Craig
中科院分区：
文献类型：
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作者：
Roy, Anirban;Hooper, D. Craig
银毛蝙蝠狂犬病毒（SHBRV）感染在宿主外周引起强烈的病毒特异性免疫反应，但由于无法打开血脑屏障（BBB）并将免疫效应器传递到中枢神经系统（CNS）组织而导致死亡是常见的。具有SJL背景的小鼠对狂犬病病毒致命感染的易感性较低。此外，已知这些动物具有下丘脑-垂体-肾上腺（HPA）轴活性降低和介导中枢神经系统炎症反应的能力升高。我们在这里表明，大约一半的PLSJL小鼠在SHBRV感染中存活下来，而这种感染对于129/SvEv小鼠来说总是致命的。这种差异与PLSJL小鼠在感染反应中介导血脑屏障通透性变化的能力升高有关。在这些动物中，诱导更广泛的血脑屏障通透性和中枢神经系统炎症导致更大的病毒清除和生存率提高。另一方面，用类固醇激素脱氢表雄酮治疗shbrv感染的PLSJL小鼠可降低血脑屏障通透性变化，并导致更高的死亡率。我们得出结论，免疫效应物在血脑屏障的浸润对狂犬病病毒感染的存活至关重要，HPA轴的活性可能影响这一过程。
Silver-haired bat rabies virus (SHBRV) infection induces a strong virus-specific immune response in the periphery of the host, but death is common due to the failure to open the blood-brain barrier (BBB) and deliver immune effectors to central nervous system (CNS) tissues. Mice with an SJL background are less susceptible to lethal infection with rabies viruses. In addition, these animals are known to have reduced hypothalamus-pituitary-adrenal (HPA) axis activity and an elevated capacity to mediate CNS inflammatory responses. We show here that approximately one-half of PLSJL mice survive an SHBRV infection that is invariably lethal for 129/SvEv mice. This difference is associated with the elevated capacity of PLSJL mice to mediate BBB permeability changes in response to the infection. The induction of more extensive BBB permeability and CNS inflammation in these animals results in greater virus clearance and improved survival. On the other hand, treatment of SHBRV-infected PLSJL mice with the steroid hormone dehydroepiandrosterone reduced BBB permeability changes and caused greater mortality. We conclude that the infiltration of immune effectors across the BBB is critical to surviving a rabies virus infection and that HPA axis activity may influence this process.