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Infection of wild-type mice by SARS-CoV-2 B.1.351 variant indicates a possible novel cross-species transmission route.
Pan, Ting; Chen, Ran; He, Xin; Yuan, Yaochang; Deng, Xiaohui; Li, Rong; Yan, Haiping; Yan, Shumei; Liu, Jun; Zhang, Yiwen; Zhang, Xiantao; Yu, Fei; Zhou, Mo; Ke, Changwen; Ma, Xiancai; Zhang, Hui.
  • Pan T; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Chen R; Center for Infection and Immunity Study, School of Medicine, Shenzhen Campus of Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.
  • He X; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Yuan Y; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Deng X; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Li R; Center for Infection and Immunity Study, School of Medicine, Shenzhen Campus of Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.
  • Yan H; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Yan S; Department of Gastroenterology, The Eighth Affiliated Hospital, Sun Yat-sen University, 518033, Shenzhen, Guangdong, China.
  • Liu J; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 510060, Guangzhou, Guangdong, China.
  • Zhang Y; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Zhang X; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Yu F; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Zhou M; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080, Guangzhou, Guangdong, China.
  • Ke C; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
  • Ma X; Guangdong Provincial Center for Disease Control and Prevention, 511430, Guangzhou, Guangdong, China.
  • Zhang H; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China. maxc6@mail.sysu.edu.cn.
Signal Transduct Target Ther ; 6(1): 420, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1585885
ABSTRACT
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Virus / Host-Pathogen Interactions / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00848-1

Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Virus / Host-Pathogen Interactions / Spike Glycoprotein, Coronavirus / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00848-1