An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines.
An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines.
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DOI：
10.1371/journal.ppat.1010828
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发表时间：
2022-09
期刊：
影响因子：
6.7
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中科院分区：
文献类型：
--
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肉瘤病毒从动物到人类的溢出已导致严重急性呼吸综合征、SARS冠状病毒的暴发和正在进行的新冠肺炎大流行。为了确定SARS-CoV-1和-2的起源，已经发现了许多动物肉瘤病毒--其中大多数只与已知的人类病原体有远亲关系，不会感染人类细胞。肉瘤病毒上的受体结合域(RBD)与宿主细胞上的受体分子结合，介导细胞侵袭。在这里，我们测试了俄罗斯马蹄蝠中发现的两种肉瘤病毒的rBDS的受体趋向性和血清学交叉反应性。虽然这两种病毒属于不同于SARS-CoV-1和SARS-2的病毒谱系，但来自一种病毒Khosta 2的RBD能够利用人类ACE2促进细胞进入。带有编码Khosta 2RBD的重组SARS-CoV-2刺突的病毒假型对SARS-CoV-2单抗和接种SARS-CoV-2疫苗的个体血清都具有耐药性。我们的发现进一步表明，在亚洲以外野生动物中传播的肉瘤病毒也对全球健康构成威胁，目前正在进行的针对新冠肺炎背后的肉瘤病毒SARS-CoV-2SARS-CoV-2的疫苗运动是在从动物来源跨物种传播后出现在人类群体中的。虽然已经发现了数百种肉瘤病毒，主要是在亚洲的蝙蝠身上，但大多数病毒不能感染人类细胞。Khosta-2是在俄罗斯发现的一种肉瘤病毒，已被证明与SARS-CoV-2相同的进入受体相互作用。在这项研究中，我们测试了这些蝙蝠病毒的刺突蛋白在不同条件下感染人类细胞的情况。我们发现，来自病毒的尖峰Khosta-2可以使用相同的进入机制感染类似于人类病原体的细胞，但对接种过SARS-CoV-2疫苗的人的血清中和具有抵抗力。
Spillover of sarbecoviruses from animals to humans has resulted in outbreaks of severe acute respiratory syndrome SARS-CoVs and the ongoing COVID-19 pandemic. Efforts to identify the origins of SARS-CoV-1 and -2 has resulted in the discovery of numerous animal sarbecoviruses–the majority of which are only distantly related to known human pathogens and do not infect human cells. The receptor binding domain (RBD) on sarbecoviruses engages receptor molecules on the host cell and mediates cell invasion. Here, we tested the receptor tropism and serological cross reactivity for RBDs from two sarbecoviruses found in Russian horseshoe bats. While these two viruses are in a viral lineage distinct from SARS-CoV-1 and -2, the RBD from one virus, Khosta 2, was capable of using human ACE2 to facilitate cell entry. Viral pseudotypes with a recombinant, SARS-CoV-2 spike encoding for the Khosta 2 RBD were resistant to both SARS-CoV-2 monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Our findings further demonstrate that sarbecoviruses circulating in wildlife outside of Asia also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2 SARS-CoV-2, the sarbecovirus behind COVID-19, emerged in the human population after cross-species transmission from an animal source. While hundreds of sarbecoviruses have been discovered, predominantly in bats in Asia, the majority are not capable of infecting human cells. Khosta-2, a sarbecovirus discovered in Russia, has been shown to interact with the same entry receptor as SARS-CoV-2. In this study, we tested how well the spike proteins from these bat viruses infect human cells under different conditions. We found that the spike from virus, Khosta-2, could infect cells similar to human pathogens using the same entry mechanisms, but was resistant to neutralization by serum from individuals who had been vaccinated for SARS-CoV-2.