Emerging SARS-CoV-2 variants expand species tropism to murines.

Emerging SARS-CoV-2 variants expand species tropism to murines.
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DOI:
10.1016/j.ebiom.2021.103643
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发表时间:
2021-11
期刊:
影响因子:
11.1
通讯作者:
Chu H
Chu H
中科院分区:
医学1区
文献类型:
--
作者:
Shuai H;Chan JF;Yuen TT;Yoon C;Hu JC;Wen L;Hu B;Yang D;Wang Y;Hou Y;Huang X;Chai Y;Chan CC;Poon VK;Lu L;Zhang RQ;Chan WM;Ip JD;Chu AW;Hu YF;Cai JP;Chan KH;Zhou J;Sridhar S;Zhang BZ;Yuan S;Zhang AJ;Huang JD;To KK;Yuen KY;Chu H

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野生型小鼠对SARS-CoV-2感染不敏感。新出现的SARS-CoV-2变体,包括B.1.1.7、B.1.351、P.1和P.3,含有与小鼠ACE2识别增加相关的spike突变,这提出了这些SARS-CoV-2变体可能已经进化到将物种倾向扩大到野生型小鼠和潜在的其他小鼠的假设。我们的研究评估了这种具有重大公共卫生重要性的可能性。在体外和体内环境下,研究了野生型(WT) SARS-CoV-2和SARS-CoV-2变体在感染小鼠(小家鼠)和大鼠(褐家鼠)中的能力。通过RT-qPCR、菌斑测定、免疫组织学染色和中和试验评估感染易感性。结果表明,B.1.1.7和其他携带n501y的变异株可以感染野生型小鼠,但WT SARS-CoV-2不能。感染后4- 7天,从接种b .1.1.7的小鼠鼻鼻甲和肺中恢复到高病毒基因组拷贝数和高传染性病毒颗粒滴度。与这些观察结果一致,接种b .1.1.7的小鼠鼻鼻甲和肺部检测到病毒核衣壳蛋白的强烈表达和组织病理学变化,而接种WT sars - cov -2的小鼠则没有。同样,B.1.1.7很容易通过产生传染性病毒颗粒感染野生型大鼠。我们的研究提供了直接证据,表明SARS-CoV-2变体B.1.1.7以及其他携带n501y的变体(包括B.1.351和P.3)已经获得了向小鼠扩展物种倾向的能力,应该实施包括严格的小鼠控制在内的公共卫生措施,以促进控制正在进行的大流行。资助本研究的机构的完整列表可以在致谢部分找到。
Wildtype mice are not susceptible to SARS-CoV-2 infection. Emerging SARS-CoV-2 variants, including B.1.1.7, B.1.351, P.1, and P.3, contain mutations in spike that has been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that these SARS-CoV-2 variants may have evolved to expand species tropism to wildtype mouse and potentially other murines. Our study evaluated this possibility with substantial public health importance. We investigated the capacity of wildtype (WT) SARS-CoV-2 and SARS-CoV-2 variants in infecting mice (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Susceptibility to infection was evaluated with RT-qPCR, plaque assays, immunohistological stainings, and neutralization assays. Our results reveal that B.1.1.7 and other N501Y-carrying variants but not WT SARS-CoV-2 can infect wildtype mice. High viral genome copies and high infectious virus particle titres are recovered from the nasal turbinate and lung of B.1.1.7-inocluated mice for 4-to-7 days post infection. In agreement with these observations, robust expression of viral nucleocapsid protein and histopathological changes are detected from the nasal turbinate and lung of B.1.1.7-inocluated mice but not that of the WT SARS-CoV-2-inoculated mice. Similarly, B.1.1.7 readily infects wildtype rats with production of infectious virus particles. Our study provides direct evidence that the SARS-CoV-2 variant, B.1.1.7, as well as other N501Y-carrying variants including B.1.351 and P.3, has gained the capability to expand species tropism to murines and public health measures including stringent murine control should be implemented to facilitate the control of the ongoing pandemic. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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