Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.

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 repres...

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Main Authors: Ben Hu, Lei-Ping Zeng, Xing-Lou Yang, Xing-Yi Ge, Wei Zhang, Bei Li, Jia-Zheng Xie, Xu-Rui Shen, Yun-Zhi Zhang, Ning Wang, Dong-Sheng Luo, Xiao-Shuang Zheng, Mei-Niang Wang, Peter Daszak, Lin-Fa Wang, Jie Cui, Zheng-Li Shi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-11-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1006698
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author Ben Hu
Lei-Ping Zeng
Xing-Lou Yang
Xing-Yi Ge
Wei Zhang
Bei Li
Jia-Zheng Xie
Xu-Rui Shen
Yun-Zhi Zhang
Ning Wang
Dong-Sheng Luo
Xiao-Shuang Zheng
Mei-Niang Wang
Peter Daszak
Lin-Fa Wang
Jie Cui
Zheng-Li Shi
author_facet Ben Hu
Lei-Ping Zeng
Xing-Lou Yang
Xing-Yi Ge
Wei Zhang
Bei Li
Jia-Zheng Xie
Xu-Rui Shen
Yun-Zhi Zhang
Ning Wang
Dong-Sheng Luo
Xiao-Shuang Zheng
Mei-Niang Wang
Peter Daszak
Lin-Fa Wang
Jie Cui
Zheng-Li Shi
author_sort Ben Hu
collection DOAJ
description 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.
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spelling doaj.art-fe3adc430fc2449c9a6ab57b9a314ecd2022-12-21T21:35:27ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-11-011311e100669810.1371/journal.ppat.1006698Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.Ben HuLei-Ping ZengXing-Lou YangXing-Yi GeWei ZhangBei LiJia-Zheng XieXu-Rui ShenYun-Zhi ZhangNing WangDong-Sheng LuoXiao-Shuang ZhengMei-Niang WangPeter DaszakLin-Fa WangJie CuiZheng-Li ShiA 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.https://doi.org/10.1371/journal.ppat.1006698
spellingShingle Ben Hu
Lei-Ping Zeng
Xing-Lou Yang
Xing-Yi Ge
Wei Zhang
Bei Li
Jia-Zheng Xie
Xu-Rui Shen
Yun-Zhi Zhang
Ning Wang
Dong-Sheng Luo
Xiao-Shuang Zheng
Mei-Niang Wang
Peter Daszak
Lin-Fa Wang
Jie Cui
Zheng-Li Shi
Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.
PLoS Pathogens
title Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.
title_full Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.
title_fullStr Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.
title_full_unstemmed Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.
title_short Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.
title_sort discovery of a rich gene pool of bat sars related coronaviruses provides new insights into the origin of sars coronavirus
url https://doi.org/10.1371/journal.ppat.1006698
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