Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome Coronavirus.
Identifieur interne : 001351 ( Main/Exploration ); précédent : 001350; suivant : 001352Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome Coronavirus.
Auteurs : Che-Man Chan [République populaire de Chine] ; Hin Chu [République populaire de Chine] ; Yixin Wang [République populaire de Chine] ; Bosco Ho-Yin Wong [République populaire de Chine] ; Xiaoyu Zhao [République populaire de Chine] ; Jie Zhou [République populaire de Chine] ; Dong Yang [République populaire de Chine] ; Sze Pui Leung [République populaire de Chine] ; Jasper Fuk-Woo Chan [République populaire de Chine] ; Man-Lung Yeung [République populaire de Chine] ; Jinghua Yan [République populaire de Chine] ; Guangwen Lu [République populaire de Chine] ; George Fu Gao [République populaire de Chine] ; Kwok-Yung Yuen [Hong Kong]Source :
- Journal of virology [ 1098-5514 ] ; 2016.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Carcinoembryonic Antigen, GPI-Linked Proteins, Receptors, Virus.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- Animals, Cell Line, Humans, Virus Attachment, Virus Internalization.
Abstract
The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface.
DOI: 10.1128/JVI.01133-16
PubMed: 27489282
Affiliations:
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Hong Kong Special Administrative Region, China Research Centre of Infection and Immunology, University of Hong Kong, Hong Kong Special Administrative Region, China Carol Yu Centre for Infection, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China Research Centre of Infection and Immunology, University of Hong Kong, Hong Kong Special Administrative Region, China Carol Yu Centre for Infection, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Yeung, Man Lung" sort="Yeung, Man Lung" uniqKey="Yeung M" 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Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Yixin" sort="Wang, Yixin" uniqKey="Wang Y" first="Yixin" last="Wang">Yixin Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Wong, Bosco Ho Yin" sort="Wong, Bosco Ho Yin" uniqKey="Wong B" first="Bosco Ho-Yin" last="Wong">Bosco Ho-Yin Wong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Xiaoyu" sort="Zhao, Xiaoyu" uniqKey="Zhao X" first="Xiaoyu" last="Zhao">Xiaoyu Zhao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Dong" sort="Yang, Dong" uniqKey="Yang D" first="Dong" last="Yang">Dong Yang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Leung, Sze Pui" sort="Leung, Sze Pui" uniqKey="Leung S" first="Sze Pui" last="Leung">Sze Pui Leung</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China Research Centre of Infection and Immunology, University of Hong Kong, Hong Kong Special Administrative Region, China Carol Yu Centre for Infection, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China Research Centre of Infection and Immunology, University of Hong Kong, Hong Kong Special Administrative Region, China Carol Yu Centre for Infection, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Yeung, Man Lung" sort="Yeung, Man Lung" uniqKey="Yeung M" first="Man-Lung" last="Yeung">Man-Lung Yeung</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name><affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name><affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Gao, George Fu" sort="Gao, George Fu" uniqKey="Gao G" first="George Fu" last="Gao">George Fu Gao</name><affiliation wicri:level="3"><nlm:affiliation>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></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 wicri:level="3"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China Research Centre of Infection and Immunology, University of Hong Kong, Hong Kong Special Administrative Region, China Carol Yu Centre for Infection, University of Hong Kong, Hong Kong Special Administrative Region, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China kyyuen@hku.hk.</nlm:affiliation><country wicri:rule="url">Hong Kong</country><wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong Special Administrative Region, China Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, China Research Centre of Infection and Immunology, University of Hong Kong, Hong Kong Special Administrative Region, China Carol Yu Centre for Infection, University of Hong Kong, Hong Kong Special Administrative Region, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou</wicri:regionArea><placeName><settlement type="city">Hangzhou</settlement><region type="province">Zhejiang</region></placeName></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Carcinoembryonic Antigen (metabolism)</term><term>Cell Line</term><term>GPI-Linked Proteins (metabolism)</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Receptors, Virus (metabolism)</term><term>Virus Attachment</term><term>Virus Internalization</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antigène carcinoembryonnaire (métabolisme)</term><term>Attachement viral</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term><term>Humains</term><term>Lignée cellulaire</term><term>Protéines liées au GPI (métabolisme)</term><term>Pénétration virale</term><term>Récepteurs viraux (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Carcinoembryonic Antigen</term><term>GPI-Linked Proteins</term><term>Receptors, Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigène carcinoembryonnaire</term><term>Protéines liées au GPI</term><term>Récepteurs viraux</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Humans</term><term>Virus Attachment</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Attachement viral</term><term>Humains</term><term>Lignée cellulaire</term><term>Pénétration virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5 coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5 overexpression significantly enhanced the attachment of MERS-CoV to the BHK21 cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was overexpressed in permissive cells, which suggested that CEACAM5 could facilitate MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS-CoV entry independently. Taken together, the results of our study identified CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS-CoV infection by augmenting the attachment of the virus to the host cell surface.</div></front></TEI><affiliations><list><country><li>Hong Kong</li><li>République populaire de Chine</li></country><region><li>Zhejiang</li></region><settlement><li>Hangzhou</li><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Chan, Che Man" sort="Chan, Che Man" uniqKey="Chan C" first="Che-Man" last="Chan">Che-Man Chan</name></noRegion><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name><name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name><name sortKey="Gao, George Fu" sort="Gao, George Fu" uniqKey="Gao G" first="George Fu" last="Gao">George Fu Gao</name><name sortKey="Leung, Sze Pui" sort="Leung, Sze Pui" uniqKey="Leung S" first="Sze Pui" last="Leung">Sze Pui Leung</name><name sortKey="Lu, Guangwen" sort="Lu, Guangwen" uniqKey="Lu G" first="Guangwen" last="Lu">Guangwen Lu</name><name sortKey="Wang, Yixin" sort="Wang, Yixin" uniqKey="Wang Y" first="Yixin" last="Wang">Yixin Wang</name><name sortKey="Wong, Bosco Ho Yin" sort="Wong, Bosco Ho Yin" uniqKey="Wong B" first="Bosco Ho-Yin" last="Wong">Bosco Ho-Yin Wong</name><name sortKey="Yan, Jinghua" sort="Yan, Jinghua" uniqKey="Yan J" first="Jinghua" last="Yan">Jinghua Yan</name><name sortKey="Yang, Dong" sort="Yang, Dong" uniqKey="Yang D" first="Dong" last="Yang">Dong Yang</name><name sortKey="Yeung, Man Lung" sort="Yeung, Man Lung" uniqKey="Yeung M" first="Man-Lung" last="Yeung">Man-Lung Yeung</name><name sortKey="Zhao, Xiaoyu" sort="Zhao, Xiaoyu" uniqKey="Zhao X" first="Xiaoyu" last="Zhao">Xiaoyu Zhao</name><name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name></country><country name="Hong Kong"><region name="Zhejiang"><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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