V and C proteins of measles virus function as virulence factors in vivo.
V and C proteins of measles virus function as virulence factors in vivo.
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DOI：
10.1006/viro.1999.0118
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发表时间：
2000-02
期刊：
影响因子：
3.7
通讯作者：
J. Patterson;Diane Thomas;H. Lewicki;M. Billeter;M. Oldstone
中科院分区：
文献类型：
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作者：
J. Patterson;Diane Thomas;H. Lewicki;M. Billeter;M. Oldstone
麻疹病毒（MV） P基因编码三种蛋白：P蛋白和两种非结构蛋白C和V。由于C和V蛋白的功能未知，我们使用由MV反向遗传系统产生的MV C （C-）和V （V-）缺失重组（F. Radecke， P. Spielhofer， H. Schnieder， K. Kaelin， M. Huber， C. Dotsch， G. Christiansen, and M. A. Billeter 1995）。Embo j . 14, 5773-5784)。与亲本疫苗株Edmonston (Ed) MV相比，两者在Vero细胞中均具有正常生长和细胞病变作用，并且在人神经母细胞瘤SK-N-MC细胞和表达MV受体CD46的小鼠原代神经元中表现出相似的生长动力学。然而，在体内，使用YAC-CD46转基因小鼠作为MV诱导的中枢神经系统疾病模型（m.b.a. Oldstone， H. Lewicki， D. Thomas, a . Tishon， S. Dales， J. Patterson， M. Manchester， D. Homann， D. Naniche, and a . Holz 1999）。Cell 98（629-640）、C-和V-病毒与wt Ed(V（+)C(+)）病毒有显著差异。只接种10(3)个Ed菌株PFU的新生小鼠在10-15天后发病并死亡。相比之下，接种10(3)或10(4)PFU的MV C-或MV -的患者表现出明显较少和较轻的临床症状，死亡率较低。要杀死大多数YAC-CD46小鼠，总共需要10(5)个PFU V-病毒，而用相应剂量的MV C-杀死的小鼠不到一半（44%）。免疫组化染色显示MV抗原C-和Ed在脑内的传播程度相似，但MV -在脑内的传播有限。V-的病毒载量和转录显著降低，而C-则没有。多种细胞因子和趋化因子在所有三种病毒中都同样上调。因此，MV C和V蛋白在体内编码毒力功能，并可能通过不同的机制起作用。
The measles virus (MV) P gene encodes three proteins: the P protein and two nonstructural proteins, C and V. Because the functions of both the C and V protein are unknown, we used MV C (C-) and V (V-) deletion recombinants generated by the MV reverse genetics system (F. Radecke, P. Spielhofer, H. Schnieder, K. Kaelin, M. Huber, C. Dotsch, G. Christiansen, and M. A. Billeter 1995. EMBO J. 14, 5773-5784). Compared to parental vaccine strain, Edmonston (Ed) MV, both had normal growth and cytopathic effects in Vero cells and showed similar growth kinetics in human neuroblastoma SK-N-MC cells and in primary mouse neurons expressing the MV receptor, CD46. However, in vivo, using YAC-CD46 transgenic mice as a model for MV induced CNS disease (M. B. A. Oldstone, H. Lewicki, D. Thomas, A. Tishon, S. Dales, J. Patterson, M. Manchester, D. Homann, D. Naniche, and A. Holz 1999. Cell 98, 629-640), C- and V- viruses differed markedly from wt Ed(V(+)C(+)) virus. Newborn mice inoculated with as little as 10(3) PFU of Ed strain became ill and died after 10-15 days. In contrast, those inoculated with 10(3) or 10(4) PFU of MV C- or MV V- showed significantly fewer and milder clinical symptoms and had a lower mortality. A total of 10(5) PFU V- virus were required to kill most YAC-CD46 mice, and less than half (44%) were killed with a corresponding dose of MV C-. Immunohistochemical staining for MV antigens showed similar extents of spread for MV C- and MV Ed but restricted spread for MV V- throughout the brain. Viral load and transcription were markedly reduced for V- but not for C-. Multiple cytokines and chemokines were equivalently upregulated for all three viruses. Therefore, MV C and V proteins encode virulence functions in vivo and likely operate via separate mechanisms.