Measles virus receptors and the pathogenesis of measles

麻疹病毒（MV）引起一种常见的急性传染病，其特征为发热、咳嗽和全身性斑丘疹。它主要针对免疫系统的细胞，并诱导严重的免疫抑制。信号淋巴细胞活化分子（SLAM ;也称为CD 150），其在免疫系统的细胞上表达，充当MV的细胞受体。在这项研究中，我们揭示了以下发现。1.麻疹患者体内很少有病毒使用CD 46，这是MV.2疫苗株的受体。MV可以通过非SLAM和CD 46依赖性途径感染SLAM阴性细胞，尽管效率不高。MV可能通过H蛋白的变化而适应使用CD 46作为替代受体。M和L蛋白的变化也可能通过促进MV在进入后步骤的复制而使MV适应在培养细胞上的有效生长。麻疹、犬瘟热和牛瘟病毒都属于麻疹病毒属。犬瘟热和牛瘟病毒分别使用狗和牛的SLAM作为细胞受体。人SLAM的V结构域对于MV受体功能是必需和充分的，并且SLAM中的位置61处的残基及其相邻残基在其与MV 6的H蛋白的相互作用中起重要作用。将小鼠SLAM的V结构域替换为相应的人源分子后，SLAM基因敲入小鼠可复制MV的嗜性。这些结果表明，SLAM是MV在体内的主要细胞受体，在MV的嗜性和发病机制中起重要作用。此外，SLAM基因敲入小鼠将被证明是一个有用的小动物模型，在阐明详细的发病机制和免疫反应，在MV感染。

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.