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Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.
PLoS Pathog. 2017 Nov; 13(11):e1006698.PP

Abstract

A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

Authors+Show Affiliations

CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.Yunnan Institute of Endemic Diseases Control and Prevention, Dali, China. Dali University, Dali, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.EcoHealth Alliance, New York, New York, United States of America.Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29190287

Citation

Hu, Ben, et al. "Discovery of a Rich Gene Pool of Bat SARS-related Coronaviruses Provides New Insights Into the Origin of SARS Coronavirus." PLoS Pathogens, vol. 13, no. 11, 2017, pp. e1006698.
Hu B, Zeng LP, Yang XL, et al. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog. 2017;13(11):e1006698.
Hu, B., Zeng, L. P., Yang, X. L., Ge, X. Y., Zhang, W., Li, B., Xie, J. Z., Shen, X. R., Zhang, Y. Z., Wang, N., Luo, D. S., Zheng, X. S., Wang, M. N., Daszak, P., Wang, L. F., Cui, J., & Shi, Z. L. (2017). Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathogens, 13(11), e1006698. https://doi.org/10.1371/journal.ppat.1006698
Hu B, et al. Discovery of a Rich Gene Pool of Bat SARS-related Coronaviruses Provides New Insights Into the Origin of SARS Coronavirus. PLoS Pathog. 2017;13(11):e1006698. PubMed PMID: 29190287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. AU - Hu,Ben, AU - Zeng,Lei-Ping, AU - Yang,Xing-Lou, AU - Ge,Xing-Yi, AU - Zhang,Wei, AU - Li,Bei, AU - Xie,Jia-Zheng, AU - Shen,Xu-Rui, AU - Zhang,Yun-Zhi, AU - Wang,Ning, AU - Luo,Dong-Sheng, AU - Zheng,Xiao-Shuang, AU - Wang,Mei-Niang, AU - Daszak,Peter, AU - Wang,Lin-Fa, AU - Cui,Jie, AU - Shi,Zheng-Li, Y1 - 2017/11/30/ PY - 2017/02/10/received PY - 2017/10/17/accepted PY - 2017/12/1/entrez PY - 2017/12/1/pubmed PY - 2017/12/15/medline SP - e1006698 EP - e1006698 JF - PLoS pathogens JO - PLoS Pathog VL - 13 IS - 11 N2 - A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/29190287/Discovery_of_a_rich_gene_pool_of_bat_SARS_related_coronaviruses_provides_new_insights_into_the_origin_of_SARS_coronavirus_ L2 - https://dx.plos.org/10.1371/journal.ppat.1006698 DB - PRIME DP - Unbound Medicine ER -