Cell tropism and pathogenesis of measles virus in monkeys.

Cell tropism and pathogenesis of measles virus in monkeys.
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DOI:
10.3389/fmicb.2012.00014
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发表时间:
2012
影响因子:
5.2
通讯作者:
Takeuchi K
Takeuchi K
中科院分区:
生物学2区
文献类型:
--
作者:
Kato SI;Nagata K;Takeuchi K

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麻疹病毒(MV)是一种有包膜的负链RNA病毒,属于副粘病毒科,麻疹病毒属,并且引起人类最具传染性的疾病之一。实验感染的非人灵长类动物被用作研究人类麻疹发病机制的动物模型。我们建立了一个基于高致病性野生型MV的反向遗传学系统。用反向遗传学产生的重组MV毒株感染猴子,能够分析MV发病机制的分子基础。通过用辅助基因表达缺陷的重组MV毒株感染猴,表明辅助基因的体内基本功能。此外,表达增强型绿色荧光蛋白的重组野生型MV菌株能够在体外和体内视觉追踪MV感染的细胞。迄今为止,已经鉴定了三种不同的分子作为MV的受体。信号淋巴细胞活化分子(Signaling lymphocyte activation molecule,SLAM,也称为CD 150),表达于免疫细胞上,是MV的主要受体。CD 46广泛表达于人和猴的所有有核细胞中,是MV疫苗和实验室适应株的受体。新鉴定的nectin-4(也称为脊髓灰质炎病毒受体样-4)是MV的上皮细胞受体。然而,最近的研究结果表明,CD 46作为MV受体在体外,但不是在体内。目前正在研究体内MV受体使用对疾病结局的影响。
Measles virus (MV) is an enveloped negative strand RNA virus belonging to the family of Paramyxoviridae, genus Morbillivirus, and causes one of the most contagious diseases in humans. Experimentally infected non-human primates are used as animal models for studies of the pathogenesis of human measles. We established a reverse genetics system based on a highly pathogenic wild-type MV. Infection of monkeys with recombinant MV strains generated by reverse genetics enabled analysis of the molecular basis of MV pathogenesis. The essential in vivo function of accessory genes was indicated by infecting monkeys with recombinant MV strains deficient in the expression of accessory genes. Furthermore, recombinant wild-type MV strains expressing enhanced green fluorescent protein enabled visual tracking of MV-infected cells in vitro and in vivo. To date, three different molecules have been identified as receptors for MV. Signaling lymphocyte activation molecule (SLAM, also called CD150), expressed on immune cells, is a major receptor for MV. CD46, ubiquitously expressed in all nucleated cells in humans and monkeys, is a receptor for vaccine and laboratory-adapted strains of MV. The newly identified nectin-4 (also called poliovirus-receptor-like-4) is an epithelial cell receptor for MV. However, recent findings have indicated that CD46 acts as an MV receptor in vitro but not in vivo. The impact of the receptor usage of MV in vivo on the disease outcome is now under investigation.
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