A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.
Vineet D Menachery1
Boyd L Yount1
Kari Debbink1,2
Sudhakar Agnihothram3
Lisa E Gralinski1
Jessica A Plante1
Rachel L Graham1
Trevor Scobey1
Xing-Yi Ge4
Eric F Donaldson1
Scott H Randell5,6
Antonio Lanzavecchia7
Wayne A Marasco8,9
Zhengli-Li Shi4
Ralph S Baric1,2
Affiliations9 institutions
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, USA.
Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Cystic Fibrosis Center, Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Institute for Research in Biomedicine, Bellinzona Institute of Microbiology, Zurich, Switzerland.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.
Group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human ACE2, replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV.
In vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis.
Method
experimental infection; pathogenesis study
Sample type
lung
Experimental system
in vivo animal experiment
Genomic Evolution1 records
Genomic EvolutionExtraction confidence 0.85
Key finding
Chimeric and full-length SHC014 bat coronaviruses were generated and phylogenetically analyzed, demonstrating genomic evolutionary relationships within group 2b coronaviruses and highlighting potential spillover risk to humans.
Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. ... MeSH term includes 'Phylogeny'.
Genes or proteins
spike
Analysis methods
reverse genetics; phylogenetic analysis
Molecular Adaptation1 records
Molecular AdaptationExtraction confidence 0.95
Key finding
The SHC014 spike protein of a bat coronavirus confers efficient use of human ACE2 and replication in human airway cells when expressed in a SARS-CoV backbone, indicating molecular adaptation permitting cross-species infectivity.
Group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV.
The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV.
Method
reverse genetics system; in vitro replication assay
Receptors
human angiotensin converting enzyme II (ACE2)
Zoonotic Surveillance1 records
Zoonotic SurveillanceExtraction confidence 0.70
Key finding
Circulation of SHC014-CoV in Chinese horseshoe bats was observed, indicating active surveillance of bat populations for SARS-like coronaviruses.
Effects of human anti-spike protein receptor binding domain antibodies on severe acute respiratory syndrome coronavirus neutralization escape and fitness.
