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.
1) Vineet Menachery
University of Texas Medical Branch
Verified email at utmb.edu
Vineet Menachery, PhD
Assistant Director, BSL3 Laboratories
• Assistant Professor, Microbiology And Immunology
2) Boyd Yount's research while affiliated with University of North Carolina at Chapel Hill and other places
3) Kari M Debbink Dept of Natural Sciences
301-860-3341 [email protected]
Main Campus Science Center, Room 23141
Lab Website
• debbinklab.weebly.com
4) Sudhakar Agnihothram's research while affiliated with U.S. Food and Drug Administration and other places
5) Jessica Plante
• Postdoctoral Fellow V, Microbiology And Immunology
• [email protected]
6) Ronald Graham
Professor of Mathematics and Computer Science, UC San Diego
Verified email at ucsd.edu - Homepage
combinatoricsgraph theorynumber theorycombinatorial geometrytheoretical computer science
7) Eric F. Donaldson, Ph.D. [email protected] https://sph.unc.edu/files/2016/03/710272645_cv1.pdf
8) Scott H Randell, PhD, Associate Professor, Marsico Lung Institute https://www.med.unc.edu/marsicolunginstitute/directory/scott-h-randell-phd-2/
9) Antonio Lanzavecchia, MD Immune Regulation Via Vela, 6
6500 Bellinzona, Switzerland https://www.irb.usi.ch/antonio-lanzavecchia
• 10) Wayne A. Marasco, MD, PhD Dana-Farber Cancer Institute Professor, Medicine, Harvard Medical School Professor, Cancer Immunology and Virology, Dana-Farber Cancer Institute
• https://www.dfhcc.harvard.edu/insider/member-detail/member/wayne-a-marasco-md-phd/
10) Z. L. Shi's research while affiliated with National University of Singapore and other places https://www.researchgate.net/scientific-contributions/14974556_Z_L_Shi
CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, USA.
CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China. [email protected].
11) Ralph Baric, PhD Professor Department of Epidemiology 3304 MHRC, School of Public Health https://www.med.unc.edu/microimm/directory/ralph-baric-phd-1/
