Differential immune recognition of LCMV nucleoprotein and glycoprotein in transgenic mice expressing LCMV cDNA genes.

Differential immune recognition of LCMV nucleoprotein and glycoprotein in transgenic mice expressing LCMV cDNA genes.
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表达 LCMV cDNA 基因的转基因小鼠中 LCMV 核蛋白和糖蛋白的差异免疫识别。

DOI:
10.1006/viro.1997.8507
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发表时间:
1997
期刊:
Virology.
影响因子:
--
通讯作者:
Southern,PJ
Southern,PJ
中科院分区:
--
文献类型:
--
作者:
Zeller,JC;Nguyen,N;Southern,PJ

文献摘要

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我们已经产生了双转基因(DT)小鼠,独立表达的核衣壳蛋白(NP)和表面糖蛋白(GP)的淋巴细胞性脉络丛脑膜炎病毒(LCMV)的cDNA基因。通过RT-PCR,这两个转基因的转录检测在脑和肾脏中的低水平,但没有观察到在胸腺。此外,在脾脏中观察到GP转基因的转录。在用外源性LCMV攻击后,在LCMV感染的DT小鼠中诱导了抗NP CTL应答,这表明尚未建立对NP的无应答性。与此相反,LCMV感染的DT小鼠在感染后第7天或第30天或体外脾细胞群扩增后对GP无反应,也未能产生任何针对GP的CTL应答。这表明病毒-中枢神经系统中诱导的免疫病理学可以通过转基因的联合表达而减少,而对单一转基因小鼠没有保护作用,单独表达NP或GP。因此,DT小鼠为相对于亲本C57 B1/6小鼠的抗LCMV免疫应答的比较研究创造了新的宿主遗传背景。
We have generated doubly transgenic (DT) mice that independently express cDNA genes for the nucleocapsid protein (NP) and the surface glycoproteins (GP) of lymphocytic choriomeningitis virus (LCMV). By RT-PCR, transcription of both transgenes was detected at low levels in brain and kidney but was not observed in the thymus. Additionally, transcription of the GP transgene was observed in the spleen. Following challenge with exogenous LCMV, an anti-NP CTL response was induced in LCMV-infected DT mice, suggesting that nonresponsiveness to NP had not been established. In contrast, LCMV-infected DT mice were nonresponsive to GP and failed to mount any CTL response against GP, either at Day 7 or Day 30 postinfection or following expansion of splenocyte populationsin vitro.A significant number (33%) of adult DT mice survived intracerebral infection with LCMV, suggesting that virus-induced immunopathology in the central nervous system can be diminished by combined expression of the transgenes whereas no protective effect was conferred on singly transgenic mice, expressing NP or GP alone. The DT mice therefore create a novel host genetic background for comparative studies of the anti-LCMV immune responses relative to parental C57Bl/6 mice.