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Nature∣ Qin Chuan Team:Elucidation on the Pathogenicity of Novel Coronavirus by Using hACE2 transgenic mice and Establishment of the International First Animal Model of Novel Coronavirus

2020年09月14日 Source:

On May 7, 2020, Qin Chuan team, from the Institute of Laboratory Animal Sciences of the Chinese Academy of Medical Sciences, jointly cooperated with other teams from National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Institute of Pathogen Biology of the Chinese Academy of Medical Sciences, Medical Molecular Biology Research Institute of the Chinese Academy of Medical Sciences. They officially published a research paper in Nature: "The Pathogenicity of SARS - CoV - 2 hACE2 in Transgenic Mice".


Animal model is one of the five main directions of the novel coronavirus scientific research. Due to the accumulation of Qinchuan team in the development and application of animal models of infectious diseases since SARS, the Ministry of Science and Technology arranged the team to lead the task of animal models. Against virus infection and replication in the body, disease, clinical symptoms and imaging, pathology and immunology reaction, and through genetically modified and humanized mice infected by coronavirus  receptors, the team firstly set up the transgenic mouse models infected by coronavirus pneumonia, breaking through the transformation of vaccines and drugs from laboratory to clinical key technical bottlenecks.
 

Angiotensin converting enzyme 2(ACE2) is the receptor of SARS-COV-infected cells, and the RBD region of virus S protein enters the cells by binding to ACE2. The team used ACE2 to develop a mouse model of SARS-COV-infected mice during SARS. The amino acid sequence of SARS-COV S protein and SARS-COV-2 S protein is approximately 76% consistent. Biological analysis has speculated that ACE2 is the same cell receptor of SARS-COV-2, but there is still a lack of conclusive evidence. The team selected ACE2 humanized transgenic mice to study the pathogenicity of SARS-COV-2. hACE2 transgenic mice infected with SARS-COV-2 showed symptoms such as weight loss, and the virus mainly replicated in the lungs of mice. The histopathological findings are typical of interstitial pneumonia, with marked infiltration of macrophages and lymphocytes in the alveolar interstitium, and macrophage aggregation in the alveolar cavity. Viral antigens are present in bronchial epithelial cells, macrophages, and alveolar epithelial cells.


For the first time, the establishment of transgenic mouse model presents the whole process to the world successfully simulating the SARS - CoV invasion and infection, replication in the body, the body's immune, pathological changes, symptoms and outcomes. They confirmed the virus invading  invasion receptors in vivo, promoting cognition to novel coronavirus etiology and pathology, and confirming pneumonia pathogen in accordance with the rule of the Koch.
 

Based on this model, according to the arrangement of the State Council, the Qinchuan team conducted a study on the transmission ability of the virus through respiratory droplets, close contact, aerosol, fecal mouth and other channels, which answered the questions of public concerns and provided a scientific basis for epidemic control, elimination of public panic and restoration of economic order. At the same time, they undertook the task of evaluating the effectiveness of the vaccines of five technical routes deployed by the joint prevention and control mechanism of the State Council, and completed the screening of more than 20 kinds of emergency drugs to serve the epidemic control and clinical treatment. The transgenic mouse model, as a special "patient" bred in the laboratory, has made an important historical contribution during the special period of tackling the epidemic.
 

Qin Chuan, professor of Institute of Laboratory Animal Sciences of the Chinese Academy of Medical Sciences, and Wu Guizhen, researcher of the Institute of Viral Disease Prevention and Control, Chinese Center for Disease Control and Prevention, are the corresponding authors of the paper. Dr. Bao Linlin and Wei Deng, Institute of Laboratory Animal Sciences of the Chinese Academy of Medical Sciences and Dr. Huang Baoying , Institute of Viral Disease Prevention and Control, Chinese Center for Disease Control and Prevention,  as well as professor GaoHong and Jiangning Liu, Institute of Laboratory Animal Sciences of the Chinese Academy of Medical Sciences, are first authors of the paper.