Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2

Liu，Donglan1; Chen，Chunke1; Chen，Dingbin1; Zhu，Airu1; Li，Fang1; Zhuang，Zhen1; Mok，Chris Ka Pun2,3; Dai，Jun4; Li，Xiaobo4; Jin，Yingkang5; Chen，Zhao1; Sun，Jing1; Wang，Yanqun1; Li，Yuming1; Zhang，Yanjun1; Wen，Liyan1; Zhang，Zhaoyong1; Zhuo，Jianfen1; Wang，Junxiang1; Ran，Wei1; Wang，Dong1; Zhang，Shengnan1; Tang，Yanhong1; Li，Suxiang1; Lai，Xiaoming1; Wei，Peilan1; Yuan，Jinwei1; Chen，Fangli1; Huang，Shuxiang4; Sun，Fangfang4; Qian，Zhaohui6; Tan，Wenjie7; Zhao，Jingxian1; Peiris，Malik8,9; Zhao，Jincun1,10,11,12,13

2023-01-24

10.1073/pnas.2202820120

Proceedings of the National Academy of Sciences of the United States of America   影响因子和分区

0027-8424

1091-6490

Human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63) are endemic causes of upper respiratory infections such as the “common cold” but may occasionally cause severe lower respiratory tract disease in the elderly and immunocompromised patients. There are no approved antiviral drugs or vaccines for these common cold coronaviruses (CCCoV). The recent emergence of COVID-19 and the possible cross-reactive antibody and T cell responses between these CCCoV and SARS-CoV-2 emphasize the need to develop experimental animal models for CCCoV. Mice are an ideal experimental animal model for such studies, but are resistant to HCoV-229E and HCoV-NL63 infections. Here, we generated 229E and NL63 mouse models by exogenous delivery of their receptors, human hAPN and hACE2 using replication-deficient adenoviruses (Ad5-hAPN and Ad5-hACE2), respectively. Ad5-hAPN- and Ad5-hACE2-sensitized IFNAR and STAT1 mice developed pneumonia characterized by inflammatory cell infiltration with virus clearance occurring 7 d post infection. Ad5-hAPN- and Ad5-hACE2-sensitized mice generated virus-specific T cells and neutralizing antibodies after 229E or NL63 infection, respectively. Remdesivir and a vaccine candidate targeting spike protein of 229E and NL63 accelerated viral clearance of virus in these mice. 229E- and NL63-infected mice were partially protected from SARS-CoV-2 infection, likely mediated by cross-reactive T cell responses. Ad5-hAPN- and Ad5-hACE2-transduced mice are useful for studying pathogenesis and immune responses induced by HCoV-229E and HCoV-NL63 infections and for validation of broadly protective vaccines, antibodies, and therapeutics against human respiratory coronaviruses including SARS-CoV-2.

HCoV-229E HCoV-NL63 mouse model SARS-CoV-2 therapeutics vaccine

英语

NI论文

通讯

Natural Science Foundation of Guangdong Province[2018A030313965];Medical Science and Technology Foundation of Guangdong Province[2020A111128008];Medical Science and Technology Foundation of Guangdong Province[2020B1111320003];Medical Science and Technology Foundation of Guangdong Province[2020B1111330001];Guangzhou Institute of Geochemistry, Chinese Academy of Sciences[2020GIRHHMS24];Medical Science and Technology Foundation of Guangdong Province[2020KZDZX1158];Guangzhou Municipal Science and Technology Project[202102010143];National Key Research and Development Program of China[2021YFC2301700];National Natural Science Foundation of China[8181101118];National Natural Science Foundation of China[81861168032];National Natural Science Foundation of China[82025001];National Natural Science Foundation of China[82100117];National Natural Science Foundation of China[91842106];Medical Science and Technology Foundation of Guangdong Province[B195001248];Guangdong Medical Research Foundation[B2022233];State Key Laboratory of Respiratory Disease[GHMJLRID-Z-202101];Ocean Park Conservation Foundation, Hong Kong[N_HKU737/18];Natural Science Foundation of Guangdong Province[ZNSA-2020013];

BIOLOGY & BIOCHEMISTRY;CLINICAL MEDICINE;MULTIDISCIPLINARY;PLANT & ANIMAL SCIENCE;ENVIRONMENT/ECOLOGY;SOCIAL SCIENCES, GENERAL;MICROBIOLOGY;ECONOMICS BUSINESS;IMMUNOLOGY;MATERIALS SCIENCE;MATHEMATICS;SPACE SCIENCE;MOLECULAR BIOLOGY & GENETICS;PHARMACOLOGY & TOXICOLOGY;CHEMISTRY;PSYCHIATRY/PSYCHOLOGY;NEUROSCIENCE & BEHAVIOR;PHYSICS;GEOSCIENCES;AGRICULTURAL SCIENCES;ENGINEERING

2-s2.0-85146531978

Scopus

1.State Key Laboratory of Respiratory Disease,National Clinical Research Center for Respiratory Disease,Guangzhou Institute of Respiratory Health,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,510182,China
2.The Jockey Club School of Public Health and Primary Care,The Chinese University of Hong Kong,Hong Kong
3.Li Ka Shing Institute of Health Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong
4.Guangzhou Customs District Technology Center,Guangzhou,510700,China
5.Pediatric Pulmonary Department,Guangzhou Women and Children's Medical Center,Guangzhou Medical University,Guangzhou,510623,China
6.NHC Key laboratory of Systems Biology of Pathogens,Institute of Pathogen Biology,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing,100176,China
7.Key Laboratory of Biosafety,National Health and Family Planning Commission,National Institute for Viral Disease Control and Prevention,Chinese center for disease control and prevention,Beijing,102206,China
8.Hong Kong University,Pasteur Research Pole,Hong Kong
9.School of Public Health,The University of Hong Kong,Hong Kong
10.Institute of Infectious Disease,Guangzhou Eighth People's Hospital of Guangzhou Medical University,Guangzhou,510060,China
11.Guangzhou Laboratory,Guangzhou,Bio-Island,510320,China
12.Shanghai Institute for Advanced Immunochemical Studies,School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China
13.National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,518112,China

Liu，Donglan,Chen，Chunke,Chen，Dingbin,et al. Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2[J]. Proceedings of the National Academy of Sciences of the United States of America,2023,120(4).

Liu，Donglan.,Chen，Chunke.,Chen，Dingbin.,Zhu，Airu.,Li，Fang.,...&Zhao，Jincun.(2023).Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America,120(4).

Liu，Donglan,et al."Mouse models susceptible to HCoV-229E and HCoV-NL63 and cross protection from challenge with SARS-CoV-2".Proceedings of the National Academy of Sciences of the United States of America 120.4(2023).