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.A...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)re plicated 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.展开更多
基金This work was supported by the National Special Research Program of China for Important Infectious Diseases(2017ZX10202102 and 2018ZX10302103)the Special 2019-nCoV Project of the National Key Research and Development Program of China(2020YFC0841400)+9 种基金the Emergency Key Program of Guangzhou Laboratory(EKPG21-24)the Special 2019-nCoV Program of the Natural Science Foundation of China(NSFC)(82041002)the Special Research and Development Program of Guangzhou(202008070010)the Important Key Program of NSFC⑻730060)to HZ This work was also supported by the National Natural Science Foundation of China(82102385)the National Postdoctoral Program for Innovative Talents of China Postdoctoral Science Foundation(BX20190398)to X.MThis work was also sup ported by the National Natural Science Foundation of China(81971918)Shenzhen Science and Technology Program(Grant Nos.JSGG20200225150431472 and JCYJ20200109142601702)the Pearl River S&T Nova Program of Guangzhou(201806010118)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(2021qntd43)to T.PThis work was supported by the National Natural Science Foundation of China(32100743,82171825)to X.H.
文摘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)re plicated 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.
