Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism
Niemann-Pick C1 Heterogeneity of Bat Cells Controls Filovirus Tropism
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DOI：
10.1016/j.celrep.2019.12.042
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发表时间：
2020-01-14
期刊：
影响因子：
8.8
通讯作者：
Takada, Ayato
中科院分区：
文献类型：
--
作者：
Takadate, Yoshihiro;Kondoh, Tatsunari;Takada, Ayato
果蝠被怀疑是丝状病毒的天然宿主，包括埃博拉病毒（EBOV）和马尔堡病毒（MARV）。然而，有趣的是，以前的研究表明，这些病毒根据蝙蝠的种类有不同的嗜性。在这里，我们展示了丝状病毒宿主范围限制的分子基础。我们发现，蝙蝠来源的细胞系FBKT 1和ZFBK 13 - 76 E分别显示出对EBOV和MARV的优先易感性，而测试的其他蝙蝠细胞系类似地感染了这两种病毒。在FBKT 1和ZFBK 13 - 76 E中，在尼曼-匹克C1（NPC 1）蛋白（与丝状病毒糖蛋白（GP）相互作用的细胞受体之一）中发现了独特的氨基酸（aa）序列。这些aa残基以及EBOV和MARV GP之间的一些aa差异对于丝状病毒的差异易感性至关重要。综上所述，我们的研究结果表明，蝙蝠NPC 1同源基因的异质性是控制丝状病毒物种特异性宿主嗜性的重要因素。
Fruit bats are suspected to be natural hosts of filoviruses, including Ebola virus (EBOV) and Marburg virus (MARV). Interestingly, however, previous studies suggest that these viruses have different tropisms depending on the bat species. Here, we show a molecular basis underlying the host-range restriction of filoviruses. We find that bat-derived cell lines FBKT1 and ZFBK13-76E show preferential susceptibility to EBOV and MARV, respectively, whereas the other bat cell lines tested are similarly infected with both viruses. In FBKT1 and ZFBK13-76E, unique amino acid (aa) sequences are found in the Niemann-Pick C1 (NPC1) protein, one of the cellular receptors interacting with the filovirus glycoprotein (GP). These aa residues, as well as a few aa differences between EBOV and MARV GPs, are crucial for the differential susceptibility to filoviruses. Taken together, our findings indicate that the heterogeneity of bat NPC1 orthologs is an important factor controlling filovirus species-specific host tropism.