fbpx

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

Cat and Mouse?' | Kaiser Health NewsAbstract

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.

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1

Figure 1. SARS-like viruses replicate in human…

 
Figure 2

Figure 2. SARS-CoV monoclonal antibodies have marginal…

 
Figure 3

Figure 3. Full-length SHC014-CoV replicates in human…

 
Figure 4

Figure 4. Emergence paradigms for coronaviruses. 

Coronavirus…

Similar articles

Cited by 388 articles

References

  1. Ge XY, et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013;503:535–538. doi: 10.1038/nature12711. - DOI PMC PubMed
  2. Yount B, et al. Reverse genetics with a full-length infectious cDNA of severe acute respiratory syndrome coronavirus. Proc. Natl. Acad. Sci. USA. 2003;100:12995–13000. doi: 10.1073/pnas.1735582100. - DOI PMC PubMed
  3. Becker MM, et al. Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice. Proc. Natl. Acad. Sci. USA. 2008;105:19944–19949. doi: 10.1073/pnas.0808116105. - DOI PMC PubMed
  4. Peiris JS, Guan Y, Yuen KY. Severe acute respiratory syndrome. Nat. Med. 2004;10:S88–S97. doi: 10.1038/nm1143. - DOI PMC PubMed
  5. Al-Tawfiq JA, et al. Surveillance for emerging respiratory viruses. Lancet Infect. Dis. 2014;14:992–1000. doi: 10.1016/S1473-3099(14)70840-0. - DOI PMC PubMed
  6. He B, et al. Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome–like coronavirus from bats in China. J. Virol. 2014;88:7070–7082. doi: 10.1128/JVI.00631-14. - DOI PMC PubMed
  7. Li F. Receptor recognition and cross-species infections of SARS coronavirus. Antiviral Res. 2013;100:246–254. doi: 10.1016/j.antiviral.2013.08.014. - DOI PMC PubMed
  8. Sheahan T, et al. Mechanisms of zoonotic severe acute respiratory syndrome coronavirus host range expansion in human airway epithelium. J. Virol. 2008;82:2274–2285. doi: 10.1128/JVI.02041-07. - DOI PMC PubMed
  9. Yoshikawa T, et al. Dynamic innate immune responses of human bronchial epithelial cells to severe acute respiratory syndrome–associated coronavirus infection. PLoS ONE. 2010;5:e8729. doi: 10.1371/journal.pone.0008729. - DOI PMC PubMed
  10. Qiu X, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014;514:47–53. doi: 10.1038/nature13777. - DOI PMC PubMed
  11. Sui J, et al. Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway. PLoS Pathog. 2008;4:e1000197. doi: 10.1371/journal.ppat.1000197. - DOI PMC PubMed
  12. Sui J, et al. Effects of human anti–spike protein receptor binding domain antibodies on severe acute respiratory syndrome coronavirus neutralization escape and fitness. J. Virol. 2014;88:13769–13780. doi: 10.1128/JVI.02232-14. - DOI PMC PubMed
  13. Rockx B, et al. Escape from human monoclonal antibody neutralization affects in vitro and in vivo fitness of severe acute respiratory syndrome coronavirus. J. Infect. Dis. 2010;201:946–955. doi: 10.1086/651022. - DOI PMC PubMed
  14. Spruth M, et al. A double-inactivated whole-virus candidate SARS coronavirus vaccine stimulates neutralizing and protective antibody responses. Vaccine. 2006;24:652–661. doi: 10.1016/j.vaccine.2005.08.055. - DOI PMC PubMed
  15. Bolles M, et al. A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. J. Virol. 2011;85:12201–12215. doi: 10.1128/JVI.06048-11. - DOI PMC PubMed
  16. Siegrist, C.-A. in Vaccines 6th edn. (eds. Plotkin, S.A., Orenstein, W.A. & Offit, P.A.) 14–32 (W.B. Saunders, 2013).
  17. Deming D, et al. Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants. PLoS Med. 2006;3:e525. doi: 10.1371/journal.pmed.0030525. - DOI PMC PubMed
  18. Graham RL, Donaldson EF, Baric RS. A decade after SARS: strategies for controlling emerging coronaviruses. Nat. Rev. Microbiol. 2013;11:836–848. doi: 10.1038/nrmicro3143. - DOI PMC PubMed
  19. Graham RL, Baric RS. Recombination, reservoirs and the modular spike: mechanisms of coronavirus cross-species transmission. J. Virol. 2010;84:3134–3146. doi: 10.1128/JVI.01394-09. - DOI PMC PubMed
  20. Agnihothram S, et al. A mouse model for betacoronavirus subgroup 2c using a bat coronavirus strain HKU5 variant. MBio. 2014;5:e00047–14. doi: 10.1128/mBio.00047-14. - DOI PMC PubMed
  21. Relman DA. Metagenomics, infectious disease diagnostics and outbreak investigations: sequence first, ask questions later? J. Am. Med. Assoc. 2013;309:1531–1532. doi: 10.1001/jama.2013.3678. - DOI PubMed
  22. Kaiser, J. Moratorium on risky virology studies leaves work at 14 institutions in limbo. ScienceInsiderhttp://news.sciencemag.org/biology/2014/11/moratorium-risky-virology-stu... (2014).
  23. Frieman M, et al. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. J. Virol. 2012;86:884–897. doi: 10.1128/JVI.05957-11. - DOI PMC PubMed
  24. Ren W, et al. Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin. J. Virol. 2008;82:1899–1907. doi: 10.1128/JVI.01085-07. - DOI PMC PubMed
  25. Sims AC, et al. Release of severe acute respiratory syndrome coronavirus nuclear import block enhances host transcription in human lung cells. J. Virol. 2013;87:3885–3902. doi: 10.1128/JVI.02520-12. - DOI PMC PubMed
  26. Fulcher ML, Gabriel S, Burns KA, Yankaskas JR, Randell SH. Well-differentiated human airway epithelial cell cultures. Methods Mol. Med. 2005;107:183–206. - PubMed
  27. Roberts Anjeanette, Deming Damon, Paddock Christopher D., Cheng Aaron, Yount Boyd, Vogel Leatrice, Herman Brian D., Sheahan Tim, Heise Mark, Genrich Gillian L., Zaki Sherif R., Baric Ralph, Subbarao Kanta. A Mouse-Adapted SARS-Coronavirus Causes Disease and Mortality in BALB/c Mice. PLoS Pathogens. 2007;3(1):e5. doi: 10.1371/journal.ppat.0030005. - DOI PMC PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/26552008/

You must be logged in to comment due to spam issues.