与 SARS-CoV-2 相关且对人体细胞具有传染性的蝙蝠冠状病毒,Nature

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与 SARS-CoV-2 相关且对人体细胞具有传染性的蝙蝠冠状病毒
Nature ( IF 50.5 ) Pub Date : 2022-02-16 , DOI: 10.1038/s41586-022-04532-4
Sarah Temmam _{1,

2} , Khamsing Vongphayloth ₃ , Eduard Baquero ₄ , Sandie Munier ₅ , Massimiliano Bonomi ₆ , Béatrice Regnault _{1,

2} , Bounsavane Douangboubpha ₇ , Yasaman Karami ₆ , Delphine Chrétien _{1,

2} , Daosavanh Sanamxay ₇ , Vilakhan Xayaphet ₇ , Phetphoumin Paphaphanh ₇ , Vincent Lacoste ₃ , Somphavanh Somlor ₃ , Khaithong Lakeomany ₃ , Nothasin Phommavanh ₃ , Philippe Pérot _{1,

2} , Océane Dehan _{5,

8} , Faustine Amara ₅ , Flora Donati _{5,

8} , Thomas Bigot _{1,

9} , Michael Nilges ₆ , Félix A Rey ₄ , Sylvie van der Werf _{5,

8} , Paul T Brey ₃ , Marc Eloit _{1,

2,

10}

Affiliation

Institut Pasteur, Université de Paris, Pathogen Discovery Laboratory, Paris, France.
Institut Pasteur, Université de Paris, The OIE Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Paris, France.
Institut Pasteur du Laos, Vientiane, Lao People's Democratic Republic.
Institut Pasteur, Université de Paris, CNRS UMR 3569, Structural Virology Unit, Paris, France.
Institut Pasteur, Université de Paris, CNRS UMR 3569, Molecular Genetics of RNA Viruses Unit, Paris, France.
Institut Pasteur, Université de Paris, CNRS UMR 3528, Structural Bioinformatics Unit, Paris, France.
Faculty of Environmental Sciences, National University of Laos, Vientiane, Lao People's Democratic Republic.
Institut Pasteur, Université de Paris, National Reference Center for Respiratory Viruses, Paris, France.
Institut Pasteur, Université de Paris, Bioinformatic and Biostatistic Hub - Computational Biology Department, Paris, France.
Ecole Nationale Vétérinaire d'Alfort, University of Paris-Est, Maisons-Alfort, France.

SARS-CoV-2 的动物宿主尚不清楚，尽管有报道称在亚洲鼻蝠^1-4中存在各种 SARS-CoV-2 相关病毒，包括来自R. affinis、RaTG13 ^5,6和穿山甲中最接近的病毒^7-9 . SARS-CoV-2 呈现出一个镶嵌基因组，不同的祖先对其做出贡献。刺突序列决定了其受体结合域 (RBD) 与细胞血管紧张素转换酶 2 (ACE2) 受体的结合亲和力和可及性，并负责宿主范围^10–12. SARS-CoV-2 祖先蝙蝠病毒在基因上与 SARS-CoV-2 接近并且能够通过人类 ACE2 途径进入人体细胞，但尚未确定，尽管它们将是了解流行病起源的关键。在这里，我们表明此类病毒确实在生活在印度支那半岛内老挝北部石灰岩岩溶地带的洞穴蝙蝠中传播。我们发现这些病毒的 RBD 与 SARS-CoV-2 的 RBD 仅在与 ACE2 的界面处有一个或两个残基不同，与 hACE2 蛋白的结合比早期人类病例中分离的 SARS-CoV-2 武汉病毒株更有效，并在人体细胞中介导 hACE2 依赖性进入和复制，这被中和 SARS-CoV-2 的抗体所抑制。这些蝙蝠病毒都没有在刺突中包含弗林蛋白酶切割位点。犀牛属在中南半岛。

"点击查看英文标题和摘要"

Bat coronaviruses related to SARS-CoV-2 and infectious for human cells

The animal reservoir of SARS-CoV-2 is unknown despite reports of various SARS-CoV-2-related viruses in Asian Rhinolophus bats^1–4, including the closest virus from R. affinis, RaTG13^5,6 and in pangolins^7–9. SARS-CoV-2 presents a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain (RBD) 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 pathway have not yet been identified, though they would be key in understanding the origin of the epidemics. Here we show that such viruses indeed circulate in cave bats living in the limestone karstic terrain in North Laos, within the Indochinese peninsula. We found that the RBDs 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 the SARS-CoV-2 Wuhan strain isolated in early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies neutralizing SARS-CoV-2. None of these bat viruses harbors a furin cleavage site in the spike. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula.

更新日期：2022-02-18

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