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A SCID mouse-human lung xenograft model of SARS-CoV-2 infection.
Fu, Wenkun; Wang, Wei; Yuan, Lunzhi; Lin, Yanzhen; Huang, Xiumin; Chen, Rirong; Cai, Minping; Liu, Che; Chen, Liqiang; Zhou, Ming; Wu, Kun; Zhao, Huan; Pan, Dequan; Ma, Jian; Hong, Junping; Zhai, Bingke; Zhang, Yali; Kong, Zhibo; Wang, Yingbin; Chen, Yixin; Yuan, Quan; Zhu, Huachen; Cheng, Tong; Guan, Yi; Xia, Ningshao.
  • Fu W; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Wang W; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Yuan L; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Lin Y; Department of Obstetrics and Gynecology, Zhongshan Hospital, Xiamen University, Xiamen 361004, P. R. China.
  • Huang X; Department of Obstetrics and Gynecology, Zhongshan Hospital, Xiamen University, Xiamen 361004, P. R. China.
  • Chen R; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China.
  • Cai M; Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P. R. China.
  • Liu C; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China.
  • Chen L; Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P. R. China.
  • Zhou M; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Wu K; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China.
  • Zhao H; Joint Institute of Virology (Shantou University and The University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, P. R. China.
  • Pan D; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Ma J; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Hong J; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Zhai B; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Zhang Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Kong Z; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Wang Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Chen Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Yuan Q; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Zhu H; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Cheng T; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Guan Y; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.
  • Xia N; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, P. R. China.
Theranostics ; 11(13): 6607-6615, 2021.
Article in English | MEDLINE | ID: covidwho-1231569
ABSTRACT
SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo.

Methods:

Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts.

Results:

Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts.

Conclusions:

These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Mucosa / Disease Models, Animal / SARS-CoV-2 / COVID-19 / Lung Type of study: Experimental Studies / Prognostic study Topics: Vaccines Limits: Animals / Humans / Male Language: English Journal: Theranostics Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Mucosa / Disease Models, Animal / SARS-CoV-2 / COVID-19 / Lung Type of study: Experimental Studies / Prognostic study Topics: Vaccines Limits: Animals / Humans / Male Language: English Journal: Theranostics Year: 2021 Document Type: Article