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A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence
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 curre...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797993/ https://www.ncbi.nlm.nih.gov/pubmed/26552008 http://dx.doi.org/10.1038/nm.3985 |
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author | Menachery, Vineet D Yount, Boyd L Debbink, Kari Agnihothram, Sudhakar Gralinski, Lisa E Plante, Jessica A 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 |
author_facet | Menachery, Vineet D Yount, Boyd L Debbink, Kari Agnihothram, Sudhakar Gralinski, Lisa E Plante, Jessica A 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 |
author_sort | Menachery, Vineet D |
collection | PubMed |
description | 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(1). Using the SARS-CoV reverse genetics system(2), 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm.3985) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4797993 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-47979932016-06-01 A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence Menachery, Vineet D Yount, Boyd L Debbink, Kari Agnihothram, Sudhakar Gralinski, Lisa E Plante, Jessica A 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 Nat Med Article 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(1). Using the SARS-CoV reverse genetics system(2), 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm.3985) contains supplementary material, which is available to authorized users. Nature Publishing Group US 2015-11-09 2015 /pmc/articles/PMC4797993/ /pubmed/26552008 http://dx.doi.org/10.1038/nm.3985 Text en © Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2015 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Article Menachery, Vineet D Yount, Boyd L Debbink, Kari Agnihothram, Sudhakar Gralinski, Lisa E Plante, Jessica A 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 |
title | A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence |
title_full | A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence |
title_fullStr | A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence |
title_full_unstemmed | A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence |
title_short | A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence |
title_sort | sars-like cluster of circulating bat coronaviruses shows potential for human emergence |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797993/ https://www.ncbi.nlm.nih.gov/pubmed/26552008 http://dx.doi.org/10.1038/nm.3985 |
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