Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor

Xing Yi Ge, Jia Lu Li, Xing Lou Yang, Aleksei A. Chmura, Guangjian Zhu, Jonathan H. Epstein, Jonna A Mazet, Ben Hu, Wei Zhang, Cheng Peng, Yu Ji Zhang, Chu Ming Luo, Bing Tan, Ning Wang, Yan Zhu, Gary Crameri, Shu Yi Zhang, Lin Fa Wang, Peter Daszak, Zheng Li Shi

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Abstract

The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.

Original languageEnglish (US)
Pages (from-to)535-538
Number of pages4
JournalNature
Volume503
Issue number7477
DOIs
StatePublished - 2013

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SARS Virus
Coronavirus
Severe Acute Respiratory Syndrome
Viruses
Pandemics
China
Viverridae
Vero Cells
Tropism
Peptidyl-Dipeptidase A
Disease Outbreaks

ASJC Scopus subject areas

  • General

Cite this

Ge, X. Y., Li, J. L., Yang, X. L., Chmura, A. A., Zhu, G., Epstein, J. H., ... Shi, Z. L. (2013). Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature, 503(7477), 535-538. https://doi.org/10.1038/nature12711

Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. / Ge, Xing Yi; Li, Jia Lu; Yang, Xing Lou; Chmura, Aleksei A.; Zhu, Guangjian; Epstein, Jonathan H.; Mazet, Jonna A; Hu, Ben; Zhang, Wei; Peng, Cheng; Zhang, Yu Ji; Luo, Chu Ming; Tan, Bing; Wang, Ning; Zhu, Yan; Crameri, Gary; Zhang, Shu Yi; Wang, Lin Fa; Daszak, Peter; Shi, Zheng Li.

In: Nature, Vol. 503, No. 7477, 2013, p. 535-538.

Research output: Contribution to journalArticle

Ge, XY, Li, JL, Yang, XL, Chmura, AA, Zhu, G, Epstein, JH, Mazet, JA, Hu, B, Zhang, W, Peng, C, Zhang, YJ, Luo, CM, Tan, B, Wang, N, Zhu, Y, Crameri, G, Zhang, SY, Wang, LF, Daszak, P & Shi, ZL 2013, 'Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor', Nature, vol. 503, no. 7477, pp. 535-538. https://doi.org/10.1038/nature12711
Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013;503(7477):535-538. https://doi.org/10.1038/nature12711
Ge, Xing Yi ; Li, Jia Lu ; Yang, Xing Lou ; Chmura, Aleksei A. ; Zhu, Guangjian ; Epstein, Jonathan H. ; Mazet, Jonna A ; Hu, Ben ; Zhang, Wei ; Peng, Cheng ; Zhang, Yu Ji ; Luo, Chu Ming ; Tan, Bing ; Wang, Ning ; Zhu, Yan ; Crameri, Gary ; Zhang, Shu Yi ; Wang, Lin Fa ; Daszak, Peter ; Shi, Zheng Li. / Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. In: Nature. 2013 ; Vol. 503, No. 7477. pp. 535-538.
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abstract = "The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history. An ongoing outbreak of Middle East respiratory syndrome coronavirus suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses, attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa, but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9{\%} sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.",
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