LOSS OF ACTIVE NEUROINVASIVENESS IN ATTENUATED STRAINS OF WEST NILE VIRUS - PATHOGENICITY IN IMMUNOCOMPETENT AND SCID MICE

LOSS OF ACTIVE NEUROINVASIVENESS IN ATTENUATED STRAINS OF WEST NILE VIRUS - PATHOGENICITY IN IMMUNOCOMPETENT AND SCID MICE
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DOI:
10.1007/bf01309481
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发表时间:
1994-01-01
影响因子:
2.7
通讯作者:
LUSTIG, S
LUSTIG, S
中科院分区:
医学4区
文献类型:
--
作者:
HALEVY, M;AKOV, Y;LUSTIG, S

文献摘要

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用幼年ICR小鼠和严重联合免疫缺陷(SCID)小鼠研究了西尼罗河病毒(WNV)及其衍生减毒株WN25和WN25A的神经致病性。WNV与WN25在血清学和RNA指纹图谱上具有相似性。与西尼罗河病毒不同的是,弱毒的囊膜蛋白在SDS-PAGE中的迁移率较低,这可能是由于N-连接的糖链的存在。3株病毒脑内接种对ICR小鼠均有致死作用,但在腹腔接种时,WNV可引起病毒血症,侵袭中枢,致死,而减毒液未见病毒血症或中枢入侵。在IP感染的小鼠中,该抗体可使诱导的抗体水平达到与WNV相当的水平,使它们对IC与野生型的攻击具有免疫力。在IP接种的SCID小鼠中,这三个菌株显示出类似的高病毒群,并持续到动物死亡。所有毒株均侵袭中枢神经系统,并以相似的高滴度在小鼠脑内增殖,但在侵袭时间上有很大差异:西尼罗河病毒侵袭SCID小鼠(和另外两个小鼠品系)中枢神经系统的时间比减毒株早得多,这表明它们侵袭组内单个小鼠脑的时间间隔很长。为SCID小鼠提供的数据表明,WN25和WN25A已经真正失去了神经侵袭特性,并且这种特性是通过特定于WNV的规定的、活跃的过程实现的。
The neuropathogenicity of West Nile virus (WNV) and two derived attenuated strains WN25 and WN25A, was studied in young adult ICR mice and in severe combined immunodeficient (SCID) mice. Similarity in serology and RNA fingerprints were found between WNV and WN25. The viral envelope proteins of the attenuates differed from WNV in their slower mobility in SDS-PAGE due probably to the presence of N-linked glycan. The three strains were lethal to ICR mice by intracerebral (IC) inoculation, but when inoculated intraperitoneally (IP), WNV caused viremia, invaded the CNS and was lethal, whereas the attenuates showed no viremia or invasion of the CNS. The attenuates elicited antibodies to comparable levels as WNV in IP-infected mice, conferring upon them immunity to IC challenge with the wild type. In IP-inoculated SCID mice the three strains exhibited similar high viremiae that lasted until death of the animals. All strains invaded the CNS and proliferated in the mouse brain to similar high titers, but differed largely in the time of invasion: WNV invaded the CNS of SCID mice (and two other mouse strains) much earlier than the attenuates, which showed large intervals in their time of invasion into individual mouse brains within the group. The data presented for SCID mice indicate that WN25 and WN25A have truly lost the neuroinvasive property, and that this property materialized by a prescribed, active process specific for WNV.