Presence of virus neutralizing antibodies in cerebral spinal fluid correlates with non-lethal rabies in dogs.
Presence of virus neutralizing antibodies in cerebral spinal fluid correlates with non-lethal rabies in dogs.
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DOI：
10.1371/journal.pntd.0002375
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发表时间：
2013
影响因子：
3.8
通讯作者：
Fu ZF
中科院分区：
文献类型：
--
作者：
Gnanadurai CW;Zhou M;He W;Leyson CM;Huang CT;Salyards G;Harvey SB;Chen Z;He B;Yang Y;Hooper DC;Dietzchold B;Fu ZF
狂犬病传统上被认为是在出现临床表现后统一致命的疾病。然而，越来越多的证据表明，非致命性感染以及弛缓性麻痹和脑炎的恢复在实验动物和人类中都有发生。实验感染野生型犬狂犬病毒（RABV, wt DRV-Mexico）的犬非致死性狂犬病感染与脑脊液（CSF）中存在高水平的病毒中和抗体（VNA）和中枢神经系统（CNS）中轻度免疫细胞积累相关。相比之下，死于狂犬病的狗在血清或脑脊液中只有很少或没有VNA，中枢神经系统有严重的炎症。接种狂犬病疫苗的狗没有出现狂犬病的临床症状，并在致命剂量的野生型DRV攻击中存活下来。免疫犬血清中检测到VNA，脑脊液中未检测到VNA。因此，VNA的存在对于抑制病毒在中枢神经系统内的传播并最终清除中枢神经系统中的病毒至关重要。wt RABV的非致死性感染与中枢神经系统中VNA的存在相关。因此，在中枢神经系统内产生VNA或VNA通过受损的血脑屏障从外周侵入中枢神经系统，对于清除中枢神经系统的病毒感染，从而防止其他致命的狂犬病毒感染是重要的。尽管越来越多的证据表明，在各种动物和人类中存在非致命性感染，甚至从临床狂犬病中康复，但不可避免的致命性仍然通常归因于狂犬病感染。本文报道了犬类的非致死性感染。感染狂犬病后幸存的狗与感染狂犬病后死亡的狗之间的显著差异在于，幸存的狗在血清和脑脊液中显示出高水平的VNA，并且在中枢神经系统中有轻微的免疫细胞积累，而死于疾病的狗在血清和脑脊液中显示出很少或没有VNA，并发展为严重的中枢神经系统炎症。考虑到VNA在清除中枢神经系统病毒中的作用，在中枢神经系统内产生VNA或VNA从外周穿过血脑屏障渗入中枢神经系统似乎对清除中枢神经系统中的病毒从而防止致命的狂犬病感染很重要。
Rabies is traditionally considered a uniformly fatal disease after onset of clinical manifestations. However, increasing evidence indicates that non-lethal infection as well as recovery from flaccid paralysis and encephalitis occurs in laboratory animals as well as humans. Non-lethal rabies infection in dogs experimentally infected with wild type dog rabies virus (RABV, wt DRV-Mexico) correlates with the presence of high level of virus neutralizing antibodies (VNA) in the cerebral spinal fluid (CSF) and mild immune cell accumulation in the central nervous system (CNS). By contrast, dogs that succumbed to rabies showed only little or no VNA in the serum or in the CSF and severe inflammation in the CNS. Dogs vaccinated with a rabies vaccine showed no clinical signs of rabies and survived challenge with a lethal dose of wild-type DRV. VNA was detected in the serum, but not in the CSF of immunized dogs. Thus the presence of VNA is critical for inhibiting virus spread within the CNS and eventually clearing the virus from the CNS. Non-lethal infection with wt RABV correlates with the presence of VNA in the CNS. Therefore production of VNA within the CNS or invasion of VNA from the periphery into the CNS via compromised blood-brain barrier is important for clearing the virus infection from CNS, thereby preventing an otherwise lethal rabies virus infection. Inexorable lethality is still commonly attributed to rabies infection, although there is increasing evidence for non-lethal infection and even recovery from clinical rabies in various animal species and humans. This paper reports non-lethal infection in dogs. The striking difference between dogs that survived a wt RABV infection and dogs that succumbed to the infection is that the surviving dogs showed high level of VNA in the serum and in the CSF, as well as mild immune cell accumulation in the CNS, whereas dogs that succumbed to disease showed little or no VNA in the serum or in the CSF and developed severe CNS inflammation. Considering the role of VNA in clearing the virus from the CNS, production of VNA within the CNS or infiltration of VNA from the periphery into the CNS across the blood-brain barrier appears to be important for clearing the virus from CNS thereby preventing a lethal rabies infection.
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巴斯德和狂犬病：1882年的采访。
影响因子：
1.4
作者：
Pasteur, L;Illo, J
通讯作者：
Illo, J
影响因子：
5
作者：
Kuang, Yi;Lackay, Sarah N.;Zhao, Ling;Fu, Zhen F.
通讯作者：
Fu, Zhen F.
影响因子：
3.2
作者：
Roy, Anirban;Hooper, D. Craig
通讯作者：
Hooper, D. Craig
影响因子：
5.4
作者：
Roy, Anirban;Hooper, D. Craig
通讯作者：
Hooper, D. Craig
影响因子：
14.5
作者：
Floris, S;Blezer, ELA;de Vries, HE
通讯作者：
de Vries, HE