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Identification of the cellular receptor for measles virus

麻疹病毒细胞受体的鉴定

基本信息

批准号：
10470079
负责人：
YANAGI Yusuke
金额：
$ 7.04万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470079/
关键词：
measles virus receptor SLAM cell fusion ウイルス受容体

项目摘要

Several years ago CD46 was identified as a cellular receptor for the Edmonston strain of measles virus, but most clinical isolates of measles virus, which are most efficiently isolated in marmoset B cell line B95a, cannot grow in many CD46^+ cell lines. Although some researchers attributed it to post-entry block in viral replication, others believed that there is a receptor other than CD46 for wild-type measles viruses. In this study, we showed that human SLAM (signaling lymphocytic activation molecule ; also known as CDw150), a recently discovered membrane glycoprotein involved in lymphocyte activation, is a cellular receptor for measles virus, including the Edmonston strain. Transfection with a human SLAM cDNA enabled nonsusceptible cell lines to bind measles virus, support measles virus replication, and develop cytopathic effects. The distribution of SLAM was consistent with the susceptibility of various cell lines to wild-type measles virus strains and with pathology of measles virus infection in humans and monkeys. By examining receptor function of various chimeric SLAM molecules, we also showed that the V domain of human SLAM is necessary and sufficient to interact with the measles virus H protein and allow measles virus entry. The identification of SLAM as a receptor for measles virus opens the way to a better understanding of pathogenesis of measles virus infection, especially measles virus-induced immunosuppression.

几年前，CD46被确定为麻疹病毒Edmonston株的细胞受体，但大多数麻疹病毒的临床分离株不能在许多CD46^+细胞系中生长，而麻疹病毒在狨猴B细胞系B95a中最有效地分离出来。尽管一些研究人员将其归因于病毒复制的进入后阻断，但其他人认为野生型麻疹病毒存在CD46以外的受体。在这项研究中，我们发现人类SLAM（信号淋巴细胞激活分子，也称为CDw150）是最近发现的一种参与淋巴细胞激活的膜糖蛋白，是麻疹病毒（包括Edmonston毒株）的细胞受体。转染人SLAM cDNA使非易感细胞系能够结合麻疹病毒，支持麻疹病毒复制，并产生细胞病变效应。SLAM的分布与各种细胞系对麻疹野生型病毒株的易感性以及人、猴麻疹病毒感染的病理一致。通过检测各种嵌合SLAM分子的受体功能，我们还发现人类SLAM的V结构域是与麻疹病毒H蛋白相互作用并允许麻疹病毒进入的必要和充分条件。SLAM作为麻疹病毒受体的鉴定为更好地理解麻疹病毒感染的发病机制，特别是麻疹病毒诱导的免疫抑制开辟了道路。