A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunity

Abstract Virus spillover remains a major challenge to public health. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) in humans remain largely unknown. Herein, we comprehensively chara...

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Main Authors: Xing-Yao Huang, Qi Chen, Meng-Xu Sun, Hang-Yu Zhou, Qing Ye, Wu Chen, Jin-Yu Peng, Yi-Ni Qi, Jun-Qiong Zhai, Ying Tian, Zi-Xin Liu, Yi-Jiao Huang, Yong-Qiang Deng, Xiao-Feng Li, Aiping Wu, Xiao Yang, Guan Yang, Yongyi Shen, Cheng-Feng Qin
Format: Article
Language:English
Published: Nature Publishing Group 2023-06-01
Series:Cell Discovery
Online Access:https://doi.org/10.1038/s41421-023-00557-9
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author Xing-Yao Huang
Qi Chen
Meng-Xu Sun
Hang-Yu Zhou
Qing Ye
Wu Chen
Jin-Yu Peng
Yi-Ni Qi
Jun-Qiong Zhai
Ying Tian
Zi-Xin Liu
Yi-Jiao Huang
Yong-Qiang Deng
Xiao-Feng Li
Aiping Wu
Xiao Yang
Guan Yang
Yongyi Shen
Cheng-Feng Qin
author_facet Xing-Yao Huang
Qi Chen
Meng-Xu Sun
Hang-Yu Zhou
Qing Ye
Wu Chen
Jin-Yu Peng
Yi-Ni Qi
Jun-Qiong Zhai
Ying Tian
Zi-Xin Liu
Yi-Jiao Huang
Yong-Qiang Deng
Xiao-Feng Li
Aiping Wu
Xiao Yang
Guan Yang
Yongyi Shen
Cheng-Feng Qin
author_sort Xing-Yao Huang
collection DOAJ
description Abstract Virus spillover remains a major challenge to public health. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) in humans remain largely unknown. Herein, we comprehensively characterized the infectivity and pathogenicity of a recent pCoV isolate (pCoV-GD01) in human cells and human tracheal epithelium organoids and established animal models in comparison with SARS-CoV-2. pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids. Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice and could transmit among cocaged hamsters. Interestingly, in vitro neutralization assays and animal heterologous challenge experiments demonstrated that preexisting immunity induced by SARS-CoV-2 infection or vaccination was sufficient to provide at least partial cross-protection against pCoV-GD01 challenge. Our results provide direct evidence supporting pCoV-GD01 as a potential human pathogen and highlight the potential spillover risk.
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spelling doaj.art-409e682627024aa0895d3ce8076824522023-06-18T11:06:18ZengNature Publishing GroupCell Discovery2056-59682023-06-019111310.1038/s41421-023-00557-9A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunityXing-Yao Huang0Qi Chen1Meng-Xu Sun2Hang-Yu Zhou3Qing Ye4Wu Chen5Jin-Yu Peng6Yi-Ni Qi7Jun-Qiong Zhai8Ying Tian9Zi-Xin Liu10Yi-Jiao Huang11Yong-Qiang Deng12Xiao-Feng Li13Aiping Wu14Xiao Yang15Guan Yang16Yongyi Shen17Cheng-Feng Qin18State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSInstitute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSGuangzhou Zoo & Guangzhou Wildlife Research CenterState Key Laboratory for Animal Disease Control and Prevention, Guangdong Laboratory for Lingnan Modern Agriculture, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of LifeomicsGuangzhou Zoo & Guangzhou Wildlife Research CenterState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSInstitute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical CollegeState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of LifeomicsState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of LifeomicsState Key Laboratory for Animal Disease Control and Prevention, Guangdong Laboratory for Lingnan Modern Agriculture, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural UniversityState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMSAbstract Virus spillover remains a major challenge to public health. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) in humans remain largely unknown. Herein, we comprehensively characterized the infectivity and pathogenicity of a recent pCoV isolate (pCoV-GD01) in human cells and human tracheal epithelium organoids and established animal models in comparison with SARS-CoV-2. pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids. Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice and could transmit among cocaged hamsters. Interestingly, in vitro neutralization assays and animal heterologous challenge experiments demonstrated that preexisting immunity induced by SARS-CoV-2 infection or vaccination was sufficient to provide at least partial cross-protection against pCoV-GD01 challenge. Our results provide direct evidence supporting pCoV-GD01 as a potential human pathogen and highlight the potential spillover risk.https://doi.org/10.1038/s41421-023-00557-9
spellingShingle Xing-Yao Huang
Qi Chen
Meng-Xu Sun
Hang-Yu Zhou
Qing Ye
Wu Chen
Jin-Yu Peng
Yi-Ni Qi
Jun-Qiong Zhai
Ying Tian
Zi-Xin Liu
Yi-Jiao Huang
Yong-Qiang Deng
Xiao-Feng Li
Aiping Wu
Xiao Yang
Guan Yang
Yongyi Shen
Cheng-Feng Qin
A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunity
Cell Discovery
title A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunity
title_full A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunity
title_fullStr A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunity
title_full_unstemmed A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunity
title_short A pangolin-origin SARS-CoV-2-related coronavirus: infectivity, pathogenicity, and cross-protection by preexisting immunity
title_sort pangolin origin sars cov 2 related coronavirus infectivity pathogenicity and cross protection by preexisting immunity
url https://doi.org/10.1038/s41421-023-00557-9
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