OmniVira

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

Xing-Yao Huang1 Qi Chen1 Meng-Xu Sun1 Hang-Yu Zhou2 Qing Ye1 Wu Chen3 Jin-Yu Peng4 Yi-Ni Qi5 Jun-Qiong Zhai3 Ying Tian1 Zi-Xin Liu1 Yi-Jiao Huang1 Yong-Qiang Deng1 Xiao-Feng Li1 Aiping Wu2 Xiao Yang5 Guan Yang6 Yongyi Shen7,8 Cheng-Feng Qin9,10
Affiliations 10 institutions
  1. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China.
  2. Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  3. Guangzhou Zoo & Guangzhou Wildlife Research Center, Guangzhou, Guangdong, China.
  4. State 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 University, Guangzhou, Guangdong, China.
  5. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
  6. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China. [email protected].
  7. State 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 University, Guangzhou, Guangdong, China. [email protected].
  8. Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, Guangzhou, Guangdong, China. [email protected].
  9. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China. [email protected].
  10. Research Unit of Discovery and Tracing of Natural Focus Diseases, Chinese Academy of Medical Sciences, Beijing, China. [email protected].
PMID37330497 DOI10.1038/s41421-023-00557-9 Year2023 Journal Cell discovery Cell Discov Languageeng Statusepublish

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.

Supporting text Virus Host Location

Evidence records

4 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type Virus Isolation
1 records
OVE7070 Virus Isolation
Key finding

An infectious SARS-CoV-2-related coronavirus, pCoV-GD01, was isolated from pangolins and characterized for infectivity and pathogenicity.

Virus
Deltacoronavirus Severe acute respiratory syndrome coronavirus 2
Host
pangolins Manidae Natural host
Location
Not specified
Supporting text

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.

Experimental Infection
3 records · 3 evidence types
Evidence type Pathogenicity Experiment
1 records
OVE7072 Pathogenicity Experiment
Key finding

Intranasal inoculation of the pangolin-origin coronavirus pCoV-GD01 caused severe lung pathological damage in hACE2 mice, demonstrating its pathogenicity in this model.

Virus
Deltacoronavirus
Host
house mouse Mus musculus Experimental system
Location
Not specified
Supporting text

Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice.

Method
intranasal inoculation | pathological examination of lung tissue
Experimental system
transgenic hACE2 mouse animal model
Evidence type Host Range Experiment
1 records
OVE7071 Host Range Experiment
Key finding

The pangolin-origin coronavirus pCoV-GD01 exhibited similar infectivity to SARS-CoV-2 in human cells and human tracheal epithelium organoids.

Virus
Deltacoronavirus Severe acute respiratory syndrome coronavirus 2
Host
human cells Homo sapiens Experimental system human Homo sapiens Experimental system pangolins Manidae Natural host
Location
Not specified
Supporting text

pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids.

Method
in vitro infection assay | comparative infectivity measurement
Sample type
cells | tracheal epithelium organoids
Experimental system
in vitro human cell culture and organoid infection system
Evidence type Experimental Transmission
1 records
OVE7073 Experimental Transmission
Key finding

The pangolin-origin coronavirus pCoV-GD01 was experimentally shown to transmit among cocaged hamsters under controlled laboratory conditions.

Virus
Deltacoronavirus
Host
hamsters Cricetinae Experimental system
Location
Not specified
Supporting text

Intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice and could transmit among cocaged hamsters.

Method
intranasal inoculation | animal co-housing transmission assay | pathological assessment
Experimental system
co-housing animal transmission model using cocaged hamsters