Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus
Identifieur interne : 002E79 ( Ncbi/Merge ); précédent : 002E78; suivant : 002E80Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus
Auteurs : Ben Hu [République populaire de Chine] ; Lei-Ping Zeng [République populaire de Chine] ; Xing-Lou Yang [République populaire de Chine] ; Xing-Yi Ge [République populaire de Chine] ; Wei Zhang [République populaire de Chine] ; Bei Li [République populaire de Chine] ; Jia-Zheng Xie [République populaire de Chine] ; Xu-Rui Shen [République populaire de Chine] ; Yun-Zhi Zhang [République populaire de Chine] ; Ning Wang [République populaire de Chine] ; Dong-Sheng Luo [République populaire de Chine] ; Xiao-Shuang Zheng [République populaire de Chine] ; Mei-Niang Wang [République populaire de Chine] ; Peter Daszak [États-Unis] ; Lin-Fa Wang [Singapour] ; Jie Cui [République populaire de Chine] ; Zheng-Li Shi [République populaire de Chine]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2017.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- genetics : Amino Acid Sequence, Genome, Viral, Recombination, Genetic, SARS Virus.
- virology : Chiroptera, Coronavirus Infections, Severe Acute Respiratory Syndrome.
- Animals, Evolution, Molecular, Gene Pool, Humans.
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,
Url:
DOI: 10.1371/journal.ppat.1006698
PubMed: 29190287
PubMed Central: 5708621
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PMC:5708621Le document en format XML
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<author><name sortKey="Luo, Dong Sheng" sort="Luo, Dong Sheng" uniqKey="Luo D" first="Dong-Sheng" last="Luo">Dong-Sheng Luo</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zheng, Xiao Shuang" sort="Zheng, Xiao Shuang" uniqKey="Zheng X" first="Xiao-Shuang" last="Zheng">Xiao-Shuang Zheng</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Mei Niang" sort="Wang, Mei Niang" uniqKey="Wang M" first="Mei-Niang" last="Wang">Mei-Niang Wang</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Daszak, Peter" sort="Daszak, Peter" uniqKey="Daszak P" first="Peter" last="Daszak">Peter Daszak</name>
<affiliation wicri:level="2"><nlm:aff id="aff004"><addr-line>EcoHealth Alliance, New York, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>EcoHealth Alliance, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name>
<affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Programme in Emerging Infectious Diseases, Duke-NUS Medical School</wicri:regionArea>
<wicri:noRegion>Duke-NUS Medical School</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cui, Jie" sort="Cui, Jie" uniqKey="Cui J" first="Jie" last="Cui">Jie Cui</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shi, Zheng Li" sort="Shi, Zheng Li" uniqKey="Shi Z" first="Zheng-Li" last="Shi">Zheng-Li Shi</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Pathogens</title>
<idno type="ISSN">1553-7366</idno>
<idno type="eISSN">1553-7374</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence (genetics)</term>
<term>Animals</term>
<term>Chiroptera (virology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Evolution, Molecular</term>
<term>Gene Pool</term>
<term>Genome, Viral (genetics)</term>
<term>Humans</term>
<term>Recombination, Genetic (genetics)</term>
<term>SARS Virus (genetics)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Chiroptera (virologie)</term>
<term>Génome viral (génétique)</term>
<term>Humains</term>
<term>Infections à coronavirus (virologie)</term>
<term>Pool des gènes</term>
<term>Recombinaison génétique (génétique)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Séquence d'acides aminés (génétique)</term>
<term>Virus du SRAS (génétique)</term>
<term>Évolution moléculaire</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Genome, Viral</term>
<term>Recombination, Genetic</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Génome viral</term>
<term>Recombinaison génétique</term>
<term>Séquence d'acides aminés</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Chiroptera</term>
<term>Infections à coronavirus</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Chiroptera</term>
<term>Coronavirus Infections</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Evolution, Molecular</term>
<term>Gene Pool</term>
<term>Humans</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Humains</term>
<term>Pool des gènes</term>
<term>Évolution moléculaire</term>
</keywords>
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<front><div type="abstract" xml:lang="en"><p>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, <italic>etc</italic>
) 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.</p>
</div>
</front>
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<author><name sortKey="Wang, Mei Niang" sort="Wang, Mei Niang" uniqKey="Wang M" first="Mei-Niang" last="Wang">Mei-Niang Wang</name>
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</nlm:aff>
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<author><name sortKey="Shi, Zheng Li" sort="Shi, Zheng Li" uniqKey="Shi Z" first="Zheng-Li" last="Shi">Zheng-Li Shi</name>
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<author><name sortKey="Zeng, Lei Ping" sort="Zeng, Lei Ping" uniqKey="Zeng L" first="Lei-Ping" last="Zeng">Lei-Ping Zeng</name>
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</nlm:aff>
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<author><name sortKey="Yang, Xing Lou" sort="Yang, Xing Lou" uniqKey="Yang X" first="Xing-Lou" last="Yang">Xing-Lou Yang</name>
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</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ge, Xing Yi" sort="Ge, Xing Yi" uniqKey="Ge X" first="Xing-Yi" last="Ge">Xing-Yi Ge</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhang, Wei" sort="Zhang, Wei" uniqKey="Zhang W" first="Wei" last="Zhang">Wei Zhang</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Bei" sort="Li, Bei" uniqKey="Li B" first="Bei" last="Li">Bei Li</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Xie, Jia Zheng" sort="Xie, Jia Zheng" uniqKey="Xie J" first="Jia-Zheng" last="Xie">Jia-Zheng Xie</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shen, Xu Rui" sort="Shen, Xu Rui" uniqKey="Shen X" first="Xu-Rui" last="Shen">Xu-Rui Shen</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhang, Yun Zhi" sort="Zhang, Yun Zhi" uniqKey="Zhang Y" first="Yun-Zhi" last="Zhang">Yun-Zhi Zhang</name>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Yunnan Institute of Endemic Diseases Control and Prevention, Dali, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Yunnan Institute of Endemic Diseases Control and Prevention, Dali</wicri:regionArea>
<wicri:noRegion>Dali</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Dali University, Dali, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Dali University, Dali</wicri:regionArea>
<wicri:noRegion>Dali</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wang, Ning" sort="Wang, Ning" uniqKey="Wang N" first="Ning" last="Wang">Ning Wang</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Luo, Dong Sheng" sort="Luo, Dong Sheng" uniqKey="Luo D" first="Dong-Sheng" last="Luo">Dong-Sheng Luo</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zheng, Xiao Shuang" sort="Zheng, Xiao Shuang" uniqKey="Zheng X" first="Xiao-Shuang" last="Zheng">Xiao-Shuang Zheng</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Mei Niang" sort="Wang, Mei Niang" uniqKey="Wang M" first="Mei-Niang" last="Wang">Mei-Niang Wang</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Daszak, Peter" sort="Daszak, Peter" uniqKey="Daszak P" first="Peter" last="Daszak">Peter Daszak</name>
<affiliation wicri:level="2"><nlm:aff id="aff004"><addr-line>EcoHealth Alliance, New York, New York, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>EcoHealth Alliance, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name>
<affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Programme in Emerging Infectious Diseases, Duke-NUS Medical School</wicri:regionArea>
<wicri:noRegion>Duke-NUS Medical School</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cui, Jie" sort="Cui, Jie" uniqKey="Cui J" first="Jie" last="Cui">Jie Cui</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shi, Zheng Li" sort="Shi, Zheng Li" uniqKey="Shi Z" first="Zheng-Li" last="Shi">Zheng-Li Shi</name>
<affiliation wicri:level="3"><nlm:aff id="aff001"><addr-line>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China</addr-line>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS Pathogens</title>
<idno type="ISSN">1553-7366</idno>
<idno type="eISSN">1553-7374</idno>
<imprint><date when="2017">2017</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p>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, <italic>etc</italic>
) 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.</p>
</div>
</front>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.</title>
<author><name sortKey="Hu, Ben" sort="Hu, Ben" uniqKey="Hu B" first="Ben" last="Hu">Ben Hu</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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</affiliation>
</author>
<author><name sortKey="Zeng, Lei Ping" sort="Zeng, Lei Ping" uniqKey="Zeng L" first="Lei-Ping" last="Zeng">Lei-Ping Zeng</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yang, Xing Lou" sort="Yang, Xing Lou" uniqKey="Yang X" first="Xing-Lou" last="Yang">Xing-Lou Yang</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ge, Xing Yi" sort="Ge, Xing Yi" uniqKey="Ge X" first="Xing-Yi" last="Ge">Xing-Yi Ge</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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</affiliation>
</author>
<author><name sortKey="Zhang, Wei" sort="Zhang, Wei" uniqKey="Zhang W" first="Wei" last="Zhang">Wei Zhang</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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</affiliation>
</author>
<author><name sortKey="Li, Bei" sort="Li, Bei" uniqKey="Li B" first="Bei" last="Li">Bei Li</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Xie, Jia Zheng" sort="Xie, Jia Zheng" uniqKey="Xie J" first="Jia-Zheng" last="Xie">Jia-Zheng Xie</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shen, Xu Rui" sort="Shen, Xu Rui" uniqKey="Shen X" first="Xu-Rui" last="Shen">Xu-Rui Shen</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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<author><name sortKey="Zhang, Yun Zhi" sort="Zhang, Yun Zhi" uniqKey="Zhang Y" first="Yun-Zhi" last="Zhang">Yun-Zhi Zhang</name>
<affiliation wicri:level="1"><nlm:affiliation>Yunnan Institute of Endemic Diseases Control and Prevention, Dali, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Yunnan Institute of Endemic Diseases Control and Prevention, Dali</wicri:regionArea>
<wicri:noRegion>Dali</wicri:noRegion>
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</author>
<author><name sortKey="Wang, Ning" sort="Wang, Ning" uniqKey="Wang N" first="Ning" last="Wang">Ning Wang</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Luo, Dong Sheng" sort="Luo, Dong Sheng" uniqKey="Luo D" first="Dong-Sheng" last="Luo">Dong-Sheng Luo</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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</author>
<author><name sortKey="Zheng, Xiao Shuang" sort="Zheng, Xiao Shuang" uniqKey="Zheng X" first="Xiao-Shuang" last="Zheng">Xiao-Shuang Zheng</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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</author>
<author><name sortKey="Wang, Mei Niang" sort="Wang, Mei Niang" uniqKey="Wang M" first="Mei-Niang" last="Wang">Mei-Niang Wang</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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<author><name sortKey="Daszak, Peter" sort="Daszak, Peter" uniqKey="Daszak P" first="Peter" last="Daszak">Peter Daszak</name>
<affiliation wicri:level="2"><nlm:affiliation>EcoHealth Alliance, New York, New York, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>EcoHealth Alliance, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
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<author><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Programme in Emerging Infectious Diseases, Duke-NUS Medical School</wicri:regionArea>
<wicri:noRegion>Duke-NUS Medical School</wicri:noRegion>
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<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
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<publicationStmt><idno type="wicri:source">PubMed</idno>
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<idno type="RBID">pubmed:29190287</idno>
<idno type="pmid">29190287</idno>
<idno type="doi">10.1371/journal.ppat.1006698</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus.</title>
<author><name sortKey="Hu, Ben" sort="Hu, Ben" uniqKey="Hu B" first="Ben" last="Hu">Ben Hu</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zeng, Lei Ping" sort="Zeng, Lei Ping" uniqKey="Zeng L" first="Lei-Ping" last="Zeng">Lei-Ping Zeng</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yang, Xing Lou" sort="Yang, Xing Lou" uniqKey="Yang X" first="Xing-Lou" last="Yang">Xing-Lou Yang</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ge, Xing Yi" sort="Ge, Xing Yi" uniqKey="Ge X" first="Xing-Yi" last="Ge">Xing-Yi Ge</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhang, Wei" sort="Zhang, Wei" uniqKey="Zhang W" first="Wei" last="Zhang">Wei Zhang</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Bei" sort="Li, Bei" uniqKey="Li B" first="Bei" last="Li">Bei Li</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Xie, Jia Zheng" sort="Xie, Jia Zheng" uniqKey="Xie J" first="Jia-Zheng" last="Xie">Jia-Zheng Xie</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shen, Xu Rui" sort="Shen, Xu Rui" uniqKey="Shen X" first="Xu-Rui" last="Shen">Xu-Rui Shen</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zhang, Yun Zhi" sort="Zhang, Yun Zhi" uniqKey="Zhang Y" first="Yun-Zhi" last="Zhang">Yun-Zhi Zhang</name>
<affiliation wicri:level="1"><nlm:affiliation>Yunnan Institute of Endemic Diseases Control and Prevention, Dali, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Yunnan Institute of Endemic Diseases Control and Prevention, Dali</wicri:regionArea>
<wicri:noRegion>Dali</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wang, Ning" sort="Wang, Ning" uniqKey="Wang N" first="Ning" last="Wang">Ning Wang</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Luo, Dong Sheng" sort="Luo, Dong Sheng" uniqKey="Luo D" first="Dong-Sheng" last="Luo">Dong-Sheng Luo</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zheng, Xiao Shuang" sort="Zheng, Xiao Shuang" uniqKey="Zheng X" first="Xiao-Shuang" last="Zheng">Xiao-Shuang Zheng</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Mei Niang" sort="Wang, Mei Niang" uniqKey="Wang M" first="Mei-Niang" last="Wang">Mei-Niang Wang</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Daszak, Peter" sort="Daszak, Peter" uniqKey="Daszak P" first="Peter" last="Daszak">Peter Daszak</name>
<affiliation wicri:level="2"><nlm:affiliation>EcoHealth Alliance, New York, New York, United States of America.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>EcoHealth Alliance, New York, New York</wicri:regionArea>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wang, Lin Fa" sort="Wang, Lin Fa" uniqKey="Wang L" first="Lin-Fa" last="Wang">Lin-Fa Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.</nlm:affiliation>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Programme in Emerging Infectious Diseases, Duke-NUS Medical School</wicri:regionArea>
<wicri:noRegion>Duke-NUS Medical School</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cui, Jie" sort="Cui, Jie" uniqKey="Cui J" first="Jie" last="Cui">Jie Cui</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Shi, Zheng Li" sort="Shi, Zheng Li" uniqKey="Shi Z" first="Zheng-Li" last="Shi">Zheng-Li Shi</name>
<affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>CAS Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases of Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">PLoS pathogens</title>
<idno type="eISSN">1553-7374</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence (genetics)</term>
<term>Animals</term>
<term>Chiroptera (virology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Evolution, Molecular</term>
<term>Gene Pool</term>
<term>Genome, Viral (genetics)</term>
<term>Humans</term>
<term>Recombination, Genetic (genetics)</term>
<term>SARS Virus (genetics)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Chiroptera (virologie)</term>
<term>Génome viral (génétique)</term>
<term>Humains</term>
<term>Infections à coronavirus (virologie)</term>
<term>Pool des gènes</term>
<term>Recombinaison génétique (génétique)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
<term>Séquence d'acides aminés (génétique)</term>
<term>Virus du SRAS (génétique)</term>
<term>Évolution moléculaire</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Genome, Viral</term>
<term>Recombination, Genetic</term>
<term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Génome viral</term>
<term>Recombinaison génétique</term>
<term>Séquence d'acides aminés</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Chiroptera</term>
<term>Infections à coronavirus</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Chiroptera</term>
<term>Coronavirus Infections</term>
<term>Severe Acute Respiratory Syndrome</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Evolution, Molecular</term>
<term>Gene Pool</term>
<term>Humans</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Humains</term>
<term>Pool des gènes</term>
<term>Évolution moléculaire</term>
</keywords>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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