A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

Vineet Menachery, Boyd L. Yount, Kari Debbink, Sudhakar Agnihothram, Lisa E. Gralinski, Jessica Plante, Rachel L. Graham, Trevor Scobey, Xing Yi Ge, Eric F. Donaldson, Scott H. Randell, Antonio Lanzavecchia, Wayne A. Marasco, Zhengli Li Shi, Ralph S. Baric

Research output: Contribution to journalArticle

77 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1508-1513
Number of pages6
JournalNature Medicine
Volume21
Issue number12
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

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Severe Acute Respiratory Syndrome
Coronavirus
Viruses
SARS Virus
Reverse Genetics
Peptidyl-Dipeptidase A
Virus Replication
Population
Disease Outbreaks
Vaccines
Monoclonal Antibodies
Lung
Infection
Proteins
In Vitro Techniques
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Menachery, V., Yount, B. L., Debbink, K., Agnihothram, S., Gralinski, L. E., Plante, J., ... Baric, R. S. (2015). A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nature Medicine, 21(12), 1508-1513. https://doi.org/10.1038/nm.3985

A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. / Menachery, Vineet; Yount, Boyd L.; Debbink, Kari; Agnihothram, Sudhakar; Gralinski, Lisa E.; Plante, Jessica; Graham, Rachel L.; Scobey, Trevor; Ge, Xing Yi; Donaldson, Eric F.; Randell, Scott H.; Lanzavecchia, Antonio; Marasco, Wayne A.; Shi, Zhengli Li; Baric, Ralph S.

In: Nature Medicine, Vol. 21, No. 12, 01.12.2015, p. 1508-1513.

Research output: Contribution to journalArticle

Menachery, V, Yount, BL, Debbink, K, Agnihothram, S, Gralinski, LE, Plante, J, Graham, RL, Scobey, T, Ge, XY, Donaldson, EF, Randell, SH, Lanzavecchia, A, Marasco, WA, Shi, ZL & Baric, RS 2015, 'A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence', Nature Medicine, vol. 21, no. 12, pp. 1508-1513. https://doi.org/10.1038/nm.3985
Menachery, Vineet ; Yount, Boyd L. ; Debbink, Kari ; Agnihothram, Sudhakar ; Gralinski, Lisa E. ; Plante, Jessica ; Graham, Rachel L. ; Scobey, Trevor ; Ge, Xing Yi ; Donaldson, Eric F. ; Randell, Scott H. ; Lanzavecchia, Antonio ; Marasco, Wayne A. ; Shi, Zhengli Li ; Baric, Ralph S. / A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. In: Nature Medicine. 2015 ; Vol. 21, No. 12. pp. 1508-1513.
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