Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin
ABSTRACT In the last 2 decades, pathogens originating in animals may have triggered three coronavirus pandemics, including the coronavirus disease 2019 pandemic. Thus, evaluation of the spillover risk of animal severe acute respiratory syndrome (SARS)-related coronavirus (SARSr-CoV) is important in...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-04-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03285-22 |
| _version_ | 1827150226986631168 |
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| author | Yong Yang Xu-Rui Shen Yu-Lan Zhang Ren-di Jiang Xi Wang Zhen-Qiong Guan Qian Li Yu-Lin Yao Qian-chun Gong Rong Geng Qi Wang Yan Zhu Jing-Yi Luo Zheng-Li Shi Hui-lan Zhang Ke Peng Peng Zhou |
| author_facet | Yong Yang Xu-Rui Shen Yu-Lan Zhang Ren-di Jiang Xi Wang Zhen-Qiong Guan Qian Li Yu-Lin Yao Qian-chun Gong Rong Geng Qi Wang Yan Zhu Jing-Yi Luo Zheng-Li Shi Hui-lan Zhang Ke Peng Peng Zhou |
| author_sort | Yong Yang |
| collection | DOAJ |
| description | ABSTRACT In the last 2 decades, pathogens originating in animals may have triggered three coronavirus pandemics, including the coronavirus disease 2019 pandemic. Thus, evaluation of the spillover risk of animal severe acute respiratory syndrome (SARS)-related coronavirus (SARSr-CoV) is important in the context of future disease preparedness. However, there is no analytical framework to assess the spillover risk of SARSr-CoVs, which cannot be determined by sequence analysis alone. Here, we established an integrity framework to evaluate the spillover risk of an animal SARSr-CoV by testing how viruses break through key human immune barriers, including viral cell tropism, replication dynamics, interferon signaling, inflammation, and adaptive immune barriers, using human ex vivo lung tissues, human airway and nasal organoids, and human lung cells. Using this framework, we showed that the two pre-emergent animal SARSr-CoVs, bat BtCoV-WIV1 and pangolin PCoV-GX, shared similar cell tropism but exhibited less replicative fitness in the human nasal cavity or airway than did SARS-CoV-2. Furthermore, these viruses triggered fewer proinflammatory responses and less cell death, yet showed interferon antagonist activity and the ability to partially escape adaptive immune barriers to SARS-CoV-2. Collectively, these animal viruses did not fully adapt to spread or cause severe diseases, thus causing successful zoonoses in humans. We believe that this experimental framework provides a path to identifying animal coronaviruses with the potential to cause future zoonoses. IMPORTANCE Evaluation of the zoonotic risk of animal SARSr-CoVs is important for future disease preparedness. However, there are misconceptions regarding the risk of animal viruses. For example, an animal SARSr-CoV could readily infect humans. Alternately, human receptor usage may result in spillover risk. Here, we established an analytical framework to assess the zoonotic risk of SARSr-CoV by testing a series of virus-host interaction profiles. Our data showed that the pre-emergent bat BtCoV-WIV1 and pangolin PCoV-GX were less adapted to humans than SARS-CoV-2 was, suggesting that it may be extremely rare for animal SARSr-CoVs to break all bottlenecks and cause successful zoonoses. |
| first_indexed | 2024-04-09T16:00:34Z |
| format | Article |
| id | doaj.art-3d493cda9b0d447d83b10055595e38c8 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2025-03-20T21:30:43Z |
| publishDate | 2023-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-3d493cda9b0d447d83b10055595e38c82024-08-11T18:27:31ZengAmerican Society for MicrobiologymBio2150-75112023-04-0114210.1128/mbio.03285-22Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and PangolinYong Yang0Xu-Rui Shen1Yu-Lan Zhang2Ren-di Jiang3Xi Wang4Zhen-Qiong Guan5Qian Li6Yu-Lin Yao7Qian-chun Gong8Rong Geng9Qi Wang10Yan Zhu11Jing-Yi Luo12Zheng-Li Shi13Hui-lan Zhang14Ke Peng15Peng Zhou16CAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaNHC Key Laboratory of Respiratory Diseases, Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaCAS Key Laboratory of Special Pathogens and State Key Laboratory of Virology, Center for Antiviral Research, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, ChinaABSTRACT In the last 2 decades, pathogens originating in animals may have triggered three coronavirus pandemics, including the coronavirus disease 2019 pandemic. Thus, evaluation of the spillover risk of animal severe acute respiratory syndrome (SARS)-related coronavirus (SARSr-CoV) is important in the context of future disease preparedness. However, there is no analytical framework to assess the spillover risk of SARSr-CoVs, which cannot be determined by sequence analysis alone. Here, we established an integrity framework to evaluate the spillover risk of an animal SARSr-CoV by testing how viruses break through key human immune barriers, including viral cell tropism, replication dynamics, interferon signaling, inflammation, and adaptive immune barriers, using human ex vivo lung tissues, human airway and nasal organoids, and human lung cells. Using this framework, we showed that the two pre-emergent animal SARSr-CoVs, bat BtCoV-WIV1 and pangolin PCoV-GX, shared similar cell tropism but exhibited less replicative fitness in the human nasal cavity or airway than did SARS-CoV-2. Furthermore, these viruses triggered fewer proinflammatory responses and less cell death, yet showed interferon antagonist activity and the ability to partially escape adaptive immune barriers to SARS-CoV-2. Collectively, these animal viruses did not fully adapt to spread or cause severe diseases, thus causing successful zoonoses in humans. We believe that this experimental framework provides a path to identifying animal coronaviruses with the potential to cause future zoonoses. IMPORTANCE Evaluation of the zoonotic risk of animal SARSr-CoVs is important for future disease preparedness. However, there are misconceptions regarding the risk of animal viruses. For example, an animal SARSr-CoV could readily infect humans. Alternately, human receptor usage may result in spillover risk. Here, we established an analytical framework to assess the zoonotic risk of SARSr-CoV by testing a series of virus-host interaction profiles. Our data showed that the pre-emergent bat BtCoV-WIV1 and pangolin PCoV-GX were less adapted to humans than SARS-CoV-2 was, suggesting that it may be extremely rare for animal SARSr-CoVs to break all bottlenecks and cause successful zoonoses.https://journals.asm.org/doi/10.1128/mbio.03285-22severe acute respiratory syndrome-related coronaviruszoonosisrisk assessmentbatpangolin |
| spellingShingle | Yong Yang Xu-Rui Shen Yu-Lan Zhang Ren-di Jiang Xi Wang Zhen-Qiong Guan Qian Li Yu-Lin Yao Qian-chun Gong Rong Geng Qi Wang Yan Zhu Jing-Yi Luo Zheng-Li Shi Hui-lan Zhang Ke Peng Peng Zhou Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin mBio severe acute respiratory syndrome-related coronavirus zoonosis risk assessment bat pangolin |
| title | Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin |
| title_full | Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin |
| title_fullStr | Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin |
| title_full_unstemmed | Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin |
| title_short | Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin |
| title_sort | strategy to assess zoonotic potential reveals low risk posed by sars related coronaviruses from bat and pangolin |
| topic | severe acute respiratory syndrome-related coronavirus zoonosis risk assessment bat pangolin |
| url | https://journals.asm.org/doi/10.1128/mbio.03285-22 |
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