title: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.
abstract: 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.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Vineet D
authors.initials: VD
authors.lastname: Menachery
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Boyd L
authors.initials: BL
authors.lastname: Yount
authors.affiliation: 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.
authors.forename: Kari
authors.initials: K
authors.lastname: Debbink
authors.affiliation: National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Agnihothram
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Gralinski
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Plante
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Graham
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Scobey
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Xing-Yi
authors.initials: XY
authors.lastname: Ge
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Eric F
authors.initials: EF
authors.lastname: Donaldson
authors.affiliation: 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.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Randell
authors.affiliation: Institute for Research in Biomedicine, Bellinzona Institute of Microbiology, Zurich, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: 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.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Zhengli-Li
authors.initials: ZL
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D002685:Chiroptera / Q000821:virology*; D058872:Epidemics; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D008168:Lung / Q000821:virology; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010802:Phylogeny; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D045169:Severe Acute Respiratory Syndrome / Q000821:virology*; D014774:Virulence; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral