Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restrictionviaTMPRSS2 activation of membrane fusion
Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restrictionviaTMPRSS2 activation of membrane fusion
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蝙蝠SARS样WIV1冠状病毒利用多种动物物种的ACE2作为受体，通过TMPRSS2激活膜融合来逃避IFITM3限制
DOI：
10.1080/22221751.2020.1787797
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发表时间：
2020
影响因子：
13.2
通讯作者：
Lin Hanxin
中科院分区：
文献类型：
--
作者：
Zheng Mei;Zhao Xuesen;Zheng Shuangli;Chen Danying;Du Pengcheng;Li Xinglin;Jiang Dong;Guo Ju-Tao;Zeng Hui;Lin Hanxin
已从蝙蝠和其他动物物种中鉴定出多种 SARS 样冠状病毒 (SL-CoV)。与 SARS-CoV 一样，一些蝙蝠 SL-CoV，例如 WIV1，也使用来自人和蝙蝠的血管紧张素转换酶 2 (ACE2) 作为进入受体。然而，这些病毒是否也可以使用其他动物物种的ACE2作为其受体仍有待确定。我们在此报告，WIV1 对 ACE2 直系同源物具有比 SARS-CoV 分离株 Tor2 更广泛的趋向性。在检查的 9 个 ACE2 直向同源物中，人类 ACE2 在介导 WIV1 假型病毒感染方面表现出最高的效率。因此，我们的研究结果表明，WIV1 有可能感染多种野生动物，并可能直接传染给人类。我们还表明，WIV1 进入细胞可能受到干扰素诱导的跨膜蛋白 (IFITM) 的限制。然而，WIV1 可以利用气道蛋白酶 TMPRSS2 来部分规避 IFITM3 限制。有趣的是，我们还发现两性霉素 B 可以通过逃避 IFITM3 介导的限制来增强 SARS-CoV 和 SL-CoV 的感染性进入。总的来说，我们的研究结果进一步强调了接触动物 SL-CoV 的风险，并强调服用两性霉素 B 的患者容易被 SL-CoV 感染，包括最近出现的 SARS-CoV-2。
Diverse SARS-like coronaviruses (SL-CoVs) have been identified from bats and other animal species. Like SARS-CoV, some bat SL-CoVs, such as WIV1, also use angiotensin converting enzyme 2 (ACE2) from human and bat as entry receptor. However, whether these viruses can also use the ACE2 of other animal species as their receptor remains to be determined. We report herein that WIV1 has a broader tropism to ACE2 orthologs than SARS-CoV isolate Tor2. Among the 9 ACE2 orthologs examined, human ACE2 exhibited the highest efficiency to mediate the infection of WIV1 pseudotyped virus. Our findings thus imply that WIV1 has the potential to infect a wide range of wild animals and may directly jump to humans. We also showed that cell entry of WIV1 could be restricted by interferon-induced transmembrane proteins (IFITMs). However, WIV1 could exploit the airway protease TMPRSS2 to partially evade the IFITM3 restriction. Interestingly, we also found that amphotericin B could enhance the infectious entry of SARS-CoVs and SL-CoVs by evading IFITM3-mediated restriction. Collectively, our findings further underscore the risk of exposure to animal SL-CoVs and highlight the vulnerability of patients who take amphotericin B to infection by SL-CoVs, including the most recently emerging (SARS-CoV-2).