CD26/DPP4 cell-surface expression in bat cells correlates with bat cell susceptibility to Middle East respiratory syndrome coronavirus (MERS-CoV) infection and evolution of persistent infection.
Identifieur interne : 001785 ( PubMed/Corpus ); précédent : 001784; suivant : 001786CD26/DPP4 cell-surface expression in bat cells correlates with bat cell susceptibility to Middle East respiratory syndrome coronavirus (MERS-CoV) infection and evolution of persistent infection.
Auteurs : Yíngyún Caì ; Shu Qìng Yú ; Elena N. Postnikova ; Steven Mazur ; John G. Bernbaum ; Robin Burk ; Téngf I Zh Ng ; Sheli R. Radoshitzky ; Marcel A. Müller ; Ingo Jordan ; Laura Bollinger ; Lisa E. Hensley ; Peter B. Jahrling ; Jens H. KuhnSource :
- PloS one [ 1932-6203 ] ; 2014.
English descriptors
- KwdEn :
- Animals, Antibodies, Monoclonal (immunology), Cell Line, Chiroptera (virology), Chlorocebus aethiops, Coronavirus Infections (transmission), Coronavirus Infections (virology), Dipeptidyl Peptidase 4 (metabolism), Disease Reservoirs (virology), Disease Susceptibility, Humans, Middle East Respiratory Syndrome Coronavirus (pathogenicity), Middle East Respiratory Syndrome Coronavirus (physiology), Receptors, Virus (metabolism), Vero Cells, Viral Tropism.
- MESH :
- chemical , immunology : Antibodies, Monoclonal.
- chemical , metabolism : Dipeptidyl Peptidase 4, Receptors, Virus.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- transmission : Coronavirus Infections.
- virology : Chiroptera, Coronavirus Infections, Disease Reservoirs.
- Animals, Cell Line, Chlorocebus aethiops, Disease Susceptibility, Humans, Vero Cells, Viral Tropism.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.
DOI: 10.1371/journal.pone.0112060
PubMed: 25409519
Links to Exploration step
pubmed:25409519Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">CD26/DPP4 cell-surface expression in bat cells correlates with bat cell susceptibility to Middle East respiratory syndrome coronavirus (MERS-CoV) infection and evolution of persistent infection.</title><author><name sortKey="Cai, Yingyun" sort="Cai, Yingyun" uniqKey="Cai Y" first="Yíngyún" last="Caì">Yíngyún Caì</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Yu, Shu Qing" sort="Yu, Shu Qing" uniqKey="Yu S" first="Shu Qìng" last="Yú">Shu Qìng Yú</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Postnikova, Elena N" sort="Postnikova, Elena N" uniqKey="Postnikova E" first="Elena N" last="Postnikova">Elena N. Postnikova</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Mazur, Steven" sort="Mazur, Steven" uniqKey="Mazur S" first="Steven" last="Mazur">Steven Mazur</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Bernbaum, John G" sort="Bernbaum, John G" uniqKey="Bernbaum J" first="John G" last="Bernbaum">John G. 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Radoshitzky</name><affiliation><nlm:affiliation>United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name><affiliation><nlm:affiliation>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Jordan, Ingo" sort="Jordan, Ingo" uniqKey="Jordan I" first="Ingo" last="Jordan">Ingo Jordan</name><affiliation><nlm:affiliation>ProBioGen AG, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Bollinger, Laura" sort="Bollinger, Laura" uniqKey="Bollinger L" first="Laura" last="Bollinger">Laura Bollinger</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E" last="Hensley">Lisa E. Hensley</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B" last="Jahrling">Peter B. Jahrling</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Kuhn, Jens H" sort="Kuhn, Jens H" uniqKey="Kuhn J" first="Jens H" last="Kuhn">Jens H. 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Postnikova</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Mazur, Steven" sort="Mazur, Steven" uniqKey="Mazur S" first="Steven" last="Mazur">Steven Mazur</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Bernbaum, John G" sort="Bernbaum, John G" uniqKey="Bernbaum J" first="John G" last="Bernbaum">John G. Bernbaum</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Burk, Robin" sort="Burk, Robin" uniqKey="Burk R" first="Robin" last="Burk">Robin Burk</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Zh Ng, Tengf I" sort="Zh Ng, Tengf I" uniqKey="Zh Ng T" first="Téngf I" last="Zh Ng">Téngf I Zh Ng</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Radoshitzky, Sheli R" sort="Radoshitzky, Sheli R" uniqKey="Radoshitzky S" first="Sheli R" last="Radoshitzky">Sheli R. Radoshitzky</name><affiliation><nlm:affiliation>United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name><affiliation><nlm:affiliation>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Jordan, Ingo" sort="Jordan, Ingo" uniqKey="Jordan I" first="Ingo" last="Jordan">Ingo Jordan</name><affiliation><nlm:affiliation>ProBioGen AG, Berlin, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Bollinger, Laura" sort="Bollinger, Laura" uniqKey="Bollinger L" first="Laura" last="Bollinger">Laura Bollinger</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Hensley, Lisa E" sort="Hensley, Lisa E" uniqKey="Hensley L" first="Lisa E" last="Hensley">Lisa E. Hensley</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Jahrling, Peter B" sort="Jahrling, Peter B" uniqKey="Jahrling P" first="Peter B" last="Jahrling">Peter B. Jahrling</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Kuhn, Jens H" sort="Kuhn, Jens H" uniqKey="Kuhn J" first="Jens H" last="Kuhn">Jens H. Kuhn</name><affiliation><nlm:affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</nlm:affiliation></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Monoclonal (immunology)</term><term>Cell Line</term><term>Chiroptera (virology)</term><term>Chlorocebus aethiops</term><term>Coronavirus Infections (transmission)</term><term>Coronavirus Infections (virology)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Disease Reservoirs (virology)</term><term>Disease Susceptibility</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Receptors, Virus (metabolism)</term><term>Vero Cells</term><term>Viral Tropism</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Receptors, Virus</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="transmission" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Chiroptera</term><term>Coronavirus Infections</term><term>Disease Reservoirs</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Chlorocebus aethiops</term><term>Disease Susceptibility</term><term>Humans</term><term>Vero Cells</term><term>Viral Tropism</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25409519</PMID><DateCompleted><Year>2015</Year><Month>07</Month><Day>09</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>10</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>11</Issue><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS ONE</ISOAbbreviation></Journal><ArticleTitle>CD26/DPP4 cell-surface expression in bat cells correlates with bat cell susceptibility to Middle East respiratory syndrome coronavirus (MERS-CoV) infection and evolution of persistent infection.</ArticleTitle><Pagination><MedlinePgn>e112060</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0112060</ELocationID><Abstract><AbstractText>Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Caì</LastName><ForeName>Yíngyún</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yú</LastName><ForeName>Shu Qìng</ForeName><Initials>SQ</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Postnikova</LastName><ForeName>Elena N</ForeName><Initials>EN</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mazur</LastName><ForeName>Steven</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bernbaum</LastName><ForeName>John G</ForeName><Initials>JG</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burk</LastName><ForeName>Robin</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhāng</LastName><ForeName>Téngfēi</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Radoshitzky</LastName><ForeName>Sheli R</ForeName><Initials>SR</Initials><AffiliationInfo><Affiliation>United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Müller</LastName><ForeName>Marcel A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jordan</LastName><ForeName>Ingo</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>ProBioGen AG, Berlin, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bollinger</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hensley</LastName><ForeName>Lisa E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jahrling</LastName><ForeName>Peter B</ForeName><Initials>PB</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kuhn</LastName><ForeName>Jens H</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>11</Month><Day>19</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS One</MedlineTA><NlmUniqueID>101285081</NlmUniqueID><ISSNLinking>1932-6203</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000911">Antibodies, Monoclonal</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011991">Receptors, Virus</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.14.5</RegistryNumber><NameOfSubstance UI="C042807">DPP4 protein, 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