CD147/EMMPRIN Acts as a Functional Entry Receptor for Measles Virus on Epithelial Cells
CD147/EMMPRIN Acts as a Functional Entry Receptor for Measles Virus on Epithelial Cells
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DOI：
10.1128/jvi.02168-09
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发表时间：
2010-05-01
影响因子：
5.4
通讯作者：
Kai, Chieko
中科院分区：
文献类型：
--
作者：
Watanabe, Akira;Yoneda, Misako;Kai, Chieko
麻疹是由麻疹病毒（MeV）引起的高度传染性人类疾病，仍然是儿童死亡的主要原因，特别是在发展中国家。野生型MeV通过使用信号传导淋巴细胞活化分子（SLAM）作为受体优先感染淋巴细胞，所述信号传导淋巴细胞活化分子（SLAM）的表达仅限于造血细胞。MeV还感染不表达SLAM的其他上皮细胞和神经元细胞，并引起肺炎和腹泻，有时会出现严重症状，如麻疹脑炎和亚急性硬化性全脑炎。MeV的组织嗜性和SLAM阳性细胞的分布之间的差异表明，有未知的受体以外的MeV的SLAM。在这里，我们确定了CD 147/EMMPRIN（细胞外基质金属蛋白酶诱导剂），一种跨膜糖蛋白，作为上皮细胞上MeV的受体。此外，我们发现亲环素B（CypB），CD 147的细胞配体，在MeV病毒粒子的掺入，并表明CypB掺入抑制显着减弱上皮细胞的SLAM非依赖性感染，而它对SLAM依赖性感染没有影响。迄今为止，MeV感染被认为是由其血凝素（H）蛋白和细胞受体结合引发的。然而，我们目前的研究表明，MeV感染也通过CD 147和病毒体相关的CypB发生，独立于MeV H。由于CD 147在多种细胞中表达，包括上皮细胞和神经元细胞，该分子可能在SLAM阴性细胞中作为MeV的进入受体。这是在单负型病毒目成员中首次报道CD 147通过在病毒体中掺入CypB而用作病毒进入受体。
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.