International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
J Virol. 2010 May;84(9):4183-93. doi: 10.1128/JVI.02168-09. Epub 2010 Feb 10.
Measles is a highly contagious human disease caused by measles virus (MeV) and remains the leading cause of death in children, particularly in developing countries. Wild-type MeV preferentially infects lymphocytes by using signaling lymphocytic activation molecule (SLAM), whose expression is restricted to hematopoietic cells, as a receptor. MeV also infects other epithelial and neuronal cells that do not express SLAM and causes pneumonia and diarrhea and, sometimes, serious symptoms such as measles encephalitis and subacute sclerosing panencephalitis. The discrepancy between the tissue tropism of MeV and the distribution of SLAM-positive cells suggests that there are unknown receptors other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix metalloproteinase inducer), a transmembrane glycoprotein, which acts as a receptor for MeV on epithelial cells. Furthermore, we found the incorporation of cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed that inhibition of CypB incorporation significantly attenuated SLAM-independent infection on epithelial cells, while it had no effect on SLAM-dependent infection. To date, MeV infection was considered to be triggered by binding of its hemagglutinin (H) protein and cellular receptors. Our present study, however, indicates that MeV infection also occurs via CD147 and virion-associated CypB, independently of MeV H. Since CD147 is expressed in a variety of cells, including epithelial and neuronal cells, this molecule possibly functions as an entry receptor for MeV in SLAM-negative cells. This is the first report among members of the Mononegavirales that CD147 is used as a virus entry receptor via incorporated CypB in the virions.
麻疹是一种由麻疹病毒（MeV）引起的高度传染性人类疾病，仍是儿童死亡的主要原因，尤其是在发展中国家。野生型 MeV 优先通过信号淋巴细胞激活分子（SLAM）感染淋巴细胞，而 SLAM 的表达仅限于造血细胞。MeV 还感染其他不表达 SLAM 的上皮细胞和神经元细胞，导致肺炎和腹泻，有时还会引起严重症状，如麻疹脑炎和亚急性硬化性全脑炎。MeV 的组织嗜性与 SLAM 阳性细胞的分布之间的差异表明，除了 SLAM 之外，还有未知的 MeV 受体。在这里，我们鉴定了 CD147/EMMPRIN（细胞外基质金属蛋白酶诱导因子），一种跨膜糖蛋白，它在上皮细胞上作为 MeV 的受体。此外，我们发现细胞色素 P450 B（CypB），一种 CD147 的细胞配体，被掺入到 MeV 病毒粒子中，并表明抑制 CypB 掺入可显著减弱上皮细胞中不依赖 SLAM 的感染，而对依赖 SLAM 的感染没有影响。迄今为止，MeV 感染被认为是通过其血凝素（H）蛋白和细胞受体的结合触发的。然而，我们目前的研究表明，MeV 感染也通过 CD147 和病毒粒子相关的 CypB 发生，而不依赖于 MeV H。由于 CD147 在多种细胞中表达，包括上皮细胞和神经元细胞，因此该分子可能作为 SLAM 阴性细胞中 MeV 的进入受体。这是 Mononegavirales 成员中首次报道 CD147 通过病毒粒子中掺入的 CypB 作为病毒进入受体。
