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，其特征是发热、咳嗽和全身性黄斑丘疹。它主要针对免疫系统的细胞，并诱导严重的免疫抑制。信号转导淋巴细胞激活分子(SLAM；又称CD150)，表达于免疫系统的细胞上，是MV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，CD46是MV2疫苗株的受体。MV可以通过不依赖SLAM和CD46的途径感染SLAM阴性细胞，尽管效率较低。MV可能通过H蛋白的改变而适应使用CD46作为替代受体。M蛋白和L蛋白的变化也可能通过促进进入后阶段的MV复制，使MV适应在培养细胞上的高效生长。麻疹、犬瘟和牛瘟病毒是莫比利病毒属的成员。犬瘟热病毒和牛瘟病毒分别以狗和牛作为细胞受体。人SLAM的V结构域是MV受体功能的必要条件和充分条件，SLAM的61位残基及其邻近残基在其与MV6 H蛋白的相互作用中起着重要作用。在SLAM敲击小鼠中，小鼠SLAM的V结构域被相应的人类分子取代后，重现了MV的趋向性。这些结果表明，SLAM是体内MV的主要细胞受体，在MV的趋向性和发病机制中起着重要作用。此外，SLAM敲门小鼠将被证明是一个有用的小动物模型，用于阐明MV感染过程中的详细发病机制和免疫反应。

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.