Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26.
Identifieur interne : 001850 ( PubMed/Corpus ); précédent : 001849; suivant : 001851Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26.
Auteurs : Qihui Wang ; Jianxun Qi ; Yuan Yuan ; Yifang Xuan ; Pengcheng Han ; Yuhua Wan ; Wei Ji ; Yan Li ; Ying Wu ; Jianwei Wang ; Aikichi Iwamoto ; Patrick C Y. Woo ; Kwok-Yung Yuen ; Jinghua Yan ; Guangwen Lu ; George F. GaoSource :
- Cell host & microbe [ 1934-6069 ] ; 2014.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Chiroptera (virology), Coronavirus (classification), Coronavirus (genetics), Coronavirus (isolation & purification), Coronavirus (metabolism), Coronavirus Infections (genetics), Coronavirus Infections (metabolism), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (genetics), Dipeptidyl Peptidase 4 (metabolism), Humans, Middle East Respiratory Syndrome Coronavirus (classification), Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (metabolism), Molecular Sequence Data, Phylogeny, Protein Binding, Receptors, Virus (chemistry), Receptors, Virus (genetics), Receptors, Virus (metabolism), Sequence Alignment, Spike Glycoprotein, Coronavirus (chemistry), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (metabolism).
- MESH :
- chemical , chemistry : Receptors, Virus, Spike Glycoprotein, Coronavirus.
- chemical , genetics : Dipeptidyl Peptidase 4, Receptors, Virus, Spike Glycoprotein, Coronavirus.
- classification : Coronavirus, Middle East Respiratory Syndrome Coronavirus.
- genetics : Coronavirus, Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus.
- isolation & purification : Coronavirus.
- metabolism : Coronavirus, Coronavirus Infections, Dipeptidyl Peptidase 4, Middle East Respiratory Syndrome Coronavirus, Receptors, Virus, Spike Glycoprotein, Coronavirus.
- virology : Chiroptera, Coronavirus Infections.
- Amino Acid Sequence, Animals, Humans, Molecular Sequence Data, Phylogeny, Protein Binding, Sequence Alignment.
Abstract
The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. However, the evolutionary pathway of MERS-CoV is still unclear. A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry. The high sequence identity in the viral spike protein prompted us to investigate if HKU4 and HKU5 can recognize hCD26 for cell entry. We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding. Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats.
DOI: 10.1016/j.chom.2014.08.009
PubMed: 25211075
Links to Exploration step
pubmed:25211075Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26.</title><author><name sortKey="Wang, Qihui" sort="Wang, Qihui" uniqKey="Wang Q" first="Qihui" last="Wang">Qihui Wang</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yuan, Yuan" sort="Yuan, Yuan" uniqKey="Yuan Y" first="Yuan" last="Yuan">Yuan Yuan</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China.</nlm:affiliation></affiliation></author><author><name sortKey="Xuan, Yifang" sort="Xuan, Yifang" uniqKey="Xuan Y" first="Yifang" last="Xuan">Yifang Xuan</name><affiliation><nlm:affiliation>Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Han, Pengcheng" sort="Han, Pengcheng" uniqKey="Han P" first="Pengcheng" last="Han">Pengcheng Han</name><affiliation><nlm:affiliation>State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wan, Yuhua" sort="Wan, Yuhua" uniqKey="Wan Y" first="Yuhua" last="Wan">Yuhua Wan</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, Anhui University, Hefei 230039, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ji, Wei" sort="Ji, Wei" uniqKey="Ji W" first="Wei" last="Ji">Wei Ji</name><affiliation><nlm:affiliation>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Ying" sort="Wu, Ying" uniqKey="Wu Y" first="Ying" last="Wu">Ying Wu</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Jianwei" sort="Wang, Jianwei" uniqKey="Wang J" first="Jianwei" last="Wang">Jianwei Wang</name><affiliation><nlm:affiliation>MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.</nlm:affiliation></affiliation></author><author><name sortKey="Iwamoto, Aikichi" sort="Iwamoto, Aikichi" uniqKey="Iwamoto A" first="Aikichi" last="Iwamoto">Aikichi Iwamoto</name><affiliation><nlm:affiliation>China-Japan Joint Laboratory of Molecular Microbiology and Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.</nlm:affiliation></affiliation></author><author><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C Y" last="Woo">Patrick C Y. Woo</name><affiliation><nlm:affiliation>State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation><nlm:affiliation>State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F" last="Gao">George F. Gao</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China; Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China; Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: gaof@im.ac.cn.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:25211075</idno><idno type="pmid">25211075</idno><idno type="doi">10.1016/j.chom.2014.08.009</idno><idno type="wicri:Area/PubMed/Corpus">001850</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001850</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26.</title><author><name sortKey="Wang, Qihui" sort="Wang, Qihui" uniqKey="Wang Q" first="Qihui" last="Wang">Qihui Wang</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Qi, Jianxun" sort="Qi, Jianxun" uniqKey="Qi J" first="Jianxun" last="Qi">Jianxun Qi</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yuan, Yuan" sort="Yuan, Yuan" uniqKey="Yuan Y" first="Yuan" last="Yuan">Yuan Yuan</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China.</nlm:affiliation></affiliation></author><author><name sortKey="Xuan, Yifang" sort="Xuan, Yifang" uniqKey="Xuan Y" first="Yifang" last="Xuan">Yifang Xuan</name><affiliation><nlm:affiliation>Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Han, Pengcheng" sort="Han, Pengcheng" uniqKey="Han P" first="Pengcheng" last="Han">Pengcheng Han</name><affiliation><nlm:affiliation>State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wan, Yuhua" sort="Wan, Yuhua" uniqKey="Wan Y" first="Yuhua" last="Wan">Yuhua Wan</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, Anhui University, Hefei 230039, China.</nlm:affiliation></affiliation></author><author><name sortKey="Ji, Wei" sort="Ji, Wei" uniqKey="Ji W" first="Wei" last="Ji">Wei Ji</name><affiliation><nlm:affiliation>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.</nlm:affiliation></affiliation></author><author><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wu, Ying" sort="Wu, Ying" uniqKey="Wu Y" first="Ying" last="Wu">Ying Wu</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Wang, Jianwei" sort="Wang, Jianwei" uniqKey="Wang J" first="Jianwei" last="Wang">Jianwei Wang</name><affiliation><nlm:affiliation>MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.</nlm:affiliation></affiliation></author><author><name sortKey="Iwamoto, Aikichi" sort="Iwamoto, Aikichi" uniqKey="Iwamoto A" first="Aikichi" last="Iwamoto">Aikichi Iwamoto</name><affiliation><nlm:affiliation>China-Japan Joint Laboratory of Molecular Microbiology and Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.</nlm:affiliation></affiliation></author><author><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C Y" last="Woo">Patrick C Y. Woo</name><affiliation><nlm:affiliation>State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation><nlm:affiliation>State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.</nlm:affiliation></affiliation></author><author><name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation></affiliation></author><author><name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F" last="Gao">George F. Gao</name><affiliation><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China; Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China; Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. Electronic address: gaof@im.ac.cn.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Cell host & microbe</title><idno type="eISSN">1934-6069</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Chiroptera (virology)</term><term>Coronavirus (classification)</term><term>Coronavirus (genetics)</term><term>Coronavirus (isolation & purification)</term><term>Coronavirus (metabolism)</term><term>Coronavirus Infections (genetics)</term><term>Coronavirus Infections (metabolism)</term><term>Coronavirus Infections (virology)</term><term>Dipeptidyl Peptidase 4 (genetics)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (classification)</term><term>Middle East Respiratory Syndrome Coronavirus (genetics)</term><term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term><term>Molecular Sequence Data</term><term>Phylogeny</term><term>Protein Binding</term><term>Receptors, Virus (chemistry)</term><term>Receptors, Virus (genetics)</term><term>Receptors, Virus (metabolism)</term><term>Sequence Alignment</term><term>Spike Glycoprotein, Coronavirus (chemistry)</term><term>Spike Glycoprotein, Coronavirus (genetics)</term><term>Spike Glycoprotein, Coronavirus (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Receptors, Virus</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Receptors, Virus</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="classification" xml:lang="en"><term>Coronavirus</term><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus</term><term>Coronavirus Infections</term><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Coronavirus</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Coronavirus</term><term>Coronavirus Infections</term><term>Dipeptidyl Peptidase 4</term><term>Middle East Respiratory Syndrome Coronavirus</term><term>Receptors, Virus</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Chiroptera</term><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Humans</term><term>Molecular Sequence Data</term><term>Phylogeny</term><term>Protein Binding</term><term>Sequence Alignment</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. However, the evolutionary pathway of MERS-CoV is still unclear. A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry. The high sequence identity in the viral spike protein prompted us to investigate if HKU4 and HKU5 can recognize hCD26 for cell entry. We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding. Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25211075</PMID><DateCompleted><Year>2015</Year><Month>06</Month><Day>16</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>01</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1934-6069</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>3</Issue><PubDate><Year>2014</Year><Month>Sep</Month><Day>10</Day></PubDate></JournalIssue><Title>Cell host & microbe</Title><ISOAbbreviation>Cell Host Microbe</ISOAbbreviation></Journal><ArticleTitle>Bat origins of MERS-CoV supported by bat coronavirus HKU4 usage of human receptor CD26.</ArticleTitle><Pagination><MedlinePgn>328-37</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.chom.2014.08.009</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1931-3128(14)00301-1</ELocationID><Abstract><AbstractText>The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. However, the evolutionary pathway of MERS-CoV is still unclear. A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry. The high sequence identity in the viral spike protein prompted us to investigate if HKU4 and HKU5 can recognize hCD26 for cell entry. We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding. Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats. </AbstractText><CopyrightInformation>Copyright © 2014 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Qihui</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qi</LastName><ForeName>Jianxun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yuan</LastName><ForeName>Yuan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xuan</LastName><ForeName>Yifang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Han</LastName><ForeName>Pengcheng</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wan</LastName><ForeName>Yuhua</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, Anhui University, Hefei 230039, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ji</LastName><ForeName>Wei</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yan</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Jianwei</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Iwamoto</LastName><ForeName>Aikichi</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>China-Japan Joint Laboratory of Molecular Microbiology and Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Woo</LastName><ForeName>Patrick C Y</ForeName><Initials>PC</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yuen</LastName><ForeName>Kwok-Yung</ForeName><Initials>KY</Initials><AffiliationInfo><Affiliation>State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region 999077, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yan</LastName><ForeName>Jinghua</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Guangwen</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>George F</ForeName><Initials>GF</Initials><AffiliationInfo><Affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui Province, China; Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China; Office of Director-General, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. 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