Bat coronaviruses related to SARS-CoV-2 and infectious for human cells
Bat coronaviruses related to SARS-CoV-2 and infectious for human cells
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DOI：
10.1038/s41586-022-04532-4
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发表时间：
2022-02-16
期刊：
影响因子：
64.8
通讯作者：
Eloit, Marc
中科院分区：
文献类型：
--
作者：
Temmam, Sarah;Vongphayloth, Khamsing;Eloit, Marc
SARS-CoV-2的动物宿主尚不清楚，尽管有报道称在亚洲菊头蝠中存在SARS-CoV-2相关病毒（1-4），包括来自R. affinis，RaTG13（refs.（5，6））和穿山甲（7-9）。SARS-CoV-2有一个镶嵌的基因组，不同的祖先贡献。刺突序列决定其受体结合结构域与细胞血管紧张素转化酶2（ACE 2）受体的结合亲和力和可及性，并负责宿主范围（10-12）。SARS-CoV-2祖先蝙蝠病毒在遗传上接近SARS-CoV-2，并且能够通过人类ACE 2（hACE 2）途径进入人类细胞，但尚未被鉴定，尽管它们将是了解流行病起源的关键。在这里，我们表明，这样的病毒循环在洞穴蝙蝠生活在石灰岩喀斯特地形在老挝北方，在印度支那半岛。我们发现这些病毒的受体结合域与SARS-CoV-2的受体结合域仅在与ACE 2的界面处有一到两个残基不同，与hACE 2蛋白的结合比从武汉早期人类病例中分离的SARS-CoV-2株更有效，并且介导hACE 2依赖性进入人类细胞并在人类细胞中复制，这被中和SARS-CoV-2的抗体抑制。这些蝙蝠病毒在刺突蛋白中都不含弗林蛋白酶切割位点。因此，我们的研究结果表明，蝙蝠传播的SARS-CoV-2样病毒对人类具有潜在的传染性，在菊头蝠属中传播。在印度支那半岛。
The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats(1-4), including the closest virus from R. affinis, RaTG13 (refs.(5,6)), and pangolins(7-9). SARS-CoV-2 has a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range(10-12). SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 (hACE2) pathway have not yet been identified, although they would be key in understanding the origin of the epidemic. Here we show that such viruses circulate in cave bats living in the limestone karstic terrain in northern Laos, in the Indochinese peninsula. We found that the receptor-binding domains of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2, bind more efficiently to the hACE2 protein than that of the SARS-CoV-2 strain isolated in Wuhan from early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies that neutralize SARS-CoV-2. None of these bat viruses contains a furin cleavage site in the spike protein. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses that are potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.