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Measles virus receptors and the pathogenesis of measles

麻疹病毒受体与麻疹发病机制

基本信息

批准号：
13226089
负责人：
YANAGI Yusuke
金额：
$ 41.34万
依托单位：
KYUSHU UNIVERCITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13226089/
关键词：
measles virus virus receptor SLAM CD150 animal model 麻疹ウイルスインターフェロンレセプター

项目摘要

Measles virus (MV) causes a common acute infectious disease characterized by fever, cough and a generalized maculopapular rash. It mainly targets cells of the immune system, and induces profound immunosuppression. Signaling lymphocyte activation molecule (SLAM ; also called CD150), which is expressed on cells of the immune system, acts as a cellular receptor for MV. In this study, we have revealed the following findings.1. Few viruses in the bodies of patients with measles use CD46, a receptor for vaccine strains of MV.2. MV can, albeit inefficiently, infect SLAM-negative cells via a SLAM-and CD46-independent pathway.3. MV may adapt to use CD46 as an alternative receptor through the changes in the H protein. The changes in M and L proteins may also allow MV to adapt to the efficient growth on cultured cells by facilitating MV replication at post-entry steps.4. Measles, canine distemper and rinderpest viruses are members of the genus Morbillivirus. Canine distemper and rinderpest viruses use dog and cow SLAM as cellular receptors, respectively.5. The V domain of the human SLAM is necessary and sufficient for MV receptor function, and a residue at position 61 and its adjacent residues in SLAM play important roles in its interaction with the H protein of MV6. SLAM knockin mice in which the V domain of mouse SLAM is replaced by the corresponding human molecule reproduce the tropism of MV.These results indicate that SLAM is the principal cellular receptor for MV in vivo, and that SLAM plays an important role in the tropism and pathogenesis of MV. Furthermore, SLAM knockin mice will prove a useful small animal model in elucidating detailed pathogenesis and immune responses during MV infection.

麻疹病毒（MV）引起一种常见的急性传染病，其特征是发烧、咳嗽和全身黄斑丘疹。它主要针对免疫系统细胞，并引起深刻的免疫抑制。信号淋巴细胞激活分子（Signaling lymphocyte activation molecule， SLAM，又称CD150）是一种表达于免疫系统细胞上的细胞受体。在这项研究中，我们揭示了以下发现。麻疹患者体内很少有病毒使用CD46，这是麻疹病毒2疫苗株的一种受体。MV可以通过不依赖于slam和cd46的途径感染slam阴性细胞，尽管效率不高。MV可能通过H蛋白的变化适应CD46作为替代受体。M和L蛋白的变化也可能通过促进MV在进入后的复制，使MV适应在培养细胞上的高效生长。麻疹、犬瘟热和牛瘟病毒是麻疹病毒属的成员。犬瘟热和牛瘟病毒分别以犬和牛的SLAM作为细胞受体。人SLAM的V结构域是MV受体功能的必要和充分条件，SLAM中61位残基及其邻近残基在其与MV6的H蛋白相互作用中起重要作用。当小鼠SLAM的V结构域被相应的人分子取代时，SLAM敲入小鼠会重现MV的向性。这些结果表明，SLAM是体内MV的主要细胞受体，并且在MV的趋向性和发病机制中起重要作用。此外，SLAM敲入小鼠将被证明是一个有用的小动物模型，用于阐明MV感染的详细发病机制和免疫反应。