Infection of wild-type mice by SARS-CoV-2 B.1.351 variant indicates a possible novel cross-species transmission route.
Infection of wild-type mice by SARS-CoV-2 B.1.351 variant indicates a possible novel cross-species transmission route.
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DOI：
10.1038/s41392-021-00848-1
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发表时间：
2021-12-14
影响因子：
39.3
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Pan T;Chen R;He X;Yuan Y;Deng X;Li R;Yan H;Yan S;Liu J;Zhang Y;Zhang X;Yu F;Zhou M;Ke C;Ma X;Zhang H
COVID-19被确定为由SARS-CoV-2引起的人畜共患疾病，它也可以交叉传播给许多动物，但不能传播给小鼠。SARS-CoV-2或小鼠的基因修饰使小鼠对病毒感染易感。虽然两者都不是自然情况，但它们目前用于建立小鼠感染模型。在这里，我们报告了野生型小鼠中SARS-CoV-2变异体B.1.351的直接接触传播。SARS-CoV-2（B.1.351）在肺和气管中有效复制并引起显著的病理变化，伴随着肺和血清中促炎细胞因子的升高。从机制上讲，SARS-CoV-2（B.1.351）刺突蛋白的受体结合结构域（RBD）与小鼠血管紧张素转换酶2（mACE 2）具有高结合亲和力，使小鼠对SARS-CoV-2（B.1.351）感染高度敏感。我们的研究表明，SARS-CoV-2（B.1.351）扩大了宿主范围，因此增加了其传播途径，而没有适应性突变。由于野生家鼠与人类生活得相当密切，这种可能的传播途径可能具有潜在风险。此外，由于SARS-CoV-2（B.1.351）是主要流行毒株之一，并且mACE 2在实验室使用的小鼠中天然表达和调节，SARS-CoV-2（B.1.351）/小鼠可以成为研究COVID-19发病机制和评估抗病毒抑制剂和疫苗的非常方便的动物模型系统。
COVID-19 is identified as a zoonotic disease caused by SARS-CoV-2, which also can cross-transmit to many animals but not mice. Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection. Although neither is the natural situation, they are currently utilized to establish mouse infection models. Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice. The SARS-CoV-2 (B.1.351) replicated efficiently and induced significant pathological changes in lungs and tracheas, accompanied by elevated proinflammatory cytokines in the lungs and sera. Mechanistically, the receptor-binding domain (RBD) of SARS-CoV-2 (B.1.351) spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2 (mACE2), allowing the mice highly susceptible to SARS-CoV-2 (B.1.351) infection. Our work suggests that SARS-CoV-2 (B.1.351) expands the host range and therefore increases its transmission route without adapted mutation. As the wild house mice live with human populations quite closely, this possible transmission route could be potentially risky. In addition, because SARS-CoV-2 (B.1.351) is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated, the SARS-CoV-2 (B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.
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影响因子：
64.5
作者：
Li Q;Nie J;Wu J;Zhang L;Ding R;Wang H;Zhang Y;Li T;Liu S;Zhang M;Zhao C;Liu H;Nie L;Qin H;Wang M;Lu Q;Li X;Liu J;Liang H;Shi Y;Shen Y;Xie L;Zhang L;Qu X;Xu W;Huang W;Wang Y
通讯作者：
Wang Y
DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
DOI：
10.1126/science.abe8499
发表时间：
2020-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou YJ;Chiba S;Halfmann P;Ehre C;Kuroda M;Dinnon KH 3rd;Leist SR;Schäfer A;Nakajima N;Takahashi K;Lee RE;Mascenik TM;Graham R;Edwards CE;Tse LV;Okuda K;Markmann AJ;Bartelt L;de Silva A;Margolis DM;Boucher RC;Randell SH;Suzuki T;Gralinski LE;Kawaoka Y;Baric RS
通讯作者：
Baric RS
影响因子：
64.5
作者：
Hoffmann M;Arora P;Groß R;Seidel A;Hörnich BF;Hahn AS;Krüger N;Graichen L;Hofmann-Winkler H;Kempf A;Winkler MS;Schulz S;Jäck HM;Jahrsdörfer B;Schrezenmeier H;Müller M;Kleger A;Münch J;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
6.4
作者：
Bao, Linlin;Gao, Hong;Qin, Chuan
通讯作者：
Qin, Chuan