Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4.
Identifieur interne : 000851 ( PubMed/Corpus ); précédent : 000850; suivant : 000852Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4.
Auteurs : Ann-Kathrin Haverkamp ; Annika Lehmbecker ; Ingo Spitzbarth ; Widagdo Widagdo ; Bart L. Haagmans ; Joaquim Segalés ; Julia Vergara-Alert ; Albert Bensaid ; Judith M A. Van Den Brand ; Albert D M E. Osterhaus ; Wolfgang Baumg RtnerSource :
- Scientific reports [ 2045-2322 ] ; 2018.
English descriptors
- KwdEn :
- Animals, Camelus, Cells, Cultured, Coronavirus Infections (metabolism), Dipeptidyl Peptidase 4 (metabolism), Fluorescent Antibody Technique, Immunohistochemistry, Keratin-14 (metabolism), Keratin-18 (metabolism), Keratin-4 (metabolism), Keratin-5 (metabolism), Microscopy, Electron, Scanning, Middle East Respiratory Syndrome Coronavirus (metabolism), Middle East Respiratory Syndrome Coronavirus (pathogenicity), Middle East Respiratory Syndrome Coronavirus (ultrastructure).
- MESH :
- chemical , metabolism : Dipeptidyl Peptidase 4, Keratin-14, Keratin-18, Keratin-4, Keratin-5.
- metabolism : Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus.
- pathogenicity : Middle East Respiratory Syndrome Coronavirus.
- ultrastructure : Middle East Respiratory Syndrome Coronavirus.
- Animals, Camelus, Cells, Cultured, Fluorescent Antibody Technique, Immunohistochemistry, Microscopy, Electron, Scanning.
Abstract
Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at day four post infection. Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14 expressing cells did not co-localize with virus. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary monocytes, but overall the expression level was lower in dromedaries. The present study underlines significant species-specific manifestations of MERS and highlights ciliary loss as an important finding in dromedaries. The obtained results promote a better understanding of coronavirus infections, which pose major health challenges.
DOI: 10.1038/s41598-018-28109-2
PubMed: 29950581
Links to Exploration step
pubmed:29950581Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4.</title><author><name sortKey="Haverkamp, Ann Kathrin" sort="Haverkamp, Ann Kathrin" uniqKey="Haverkamp A" first="Ann-Kathrin" last="Haverkamp">Ann-Kathrin Haverkamp</name><affiliation><nlm:affiliation>Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Lehmbecker, Annika" sort="Lehmbecker, Annika" uniqKey="Lehmbecker A" first="Annika" last="Lehmbecker">Annika Lehmbecker</name><affiliation><nlm:affiliation>Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Spitzbarth, Ingo" sort="Spitzbarth, Ingo" uniqKey="Spitzbarth I" first="Ingo" last="Spitzbarth">Ingo Spitzbarth</name><affiliation><nlm:affiliation>Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Widagdo, Widagdo" sort="Widagdo, Widagdo" uniqKey="Widagdo W" first="Widagdo" last="Widagdo">Widagdo Widagdo</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Haagmans, Bart L" sort="Haagmans, Bart L" uniqKey="Haagmans B" first="Bart L" last="Haagmans">Bart L. Haagmans</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Segales, Joaquim" sort="Segales, Joaquim" uniqKey="Segales J" first="Joaquim" last="Segalés">Joaquim Segalés</name><affiliation><nlm:affiliation>IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Vergara Alert, Julia" sort="Vergara Alert, Julia" uniqKey="Vergara Alert J" first="Julia" last="Vergara-Alert">Julia Vergara-Alert</name><affiliation><nlm:affiliation>IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Bensaid, Albert" sort="Bensaid, Albert" uniqKey="Bensaid A" first="Albert" last="Bensaid">Albert Bensaid</name><affiliation><nlm:affiliation>IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Van Den Brand, Judith M A" sort="Van Den Brand, Judith M A" uniqKey="Van Den Brand J" first="Judith M A" last="Van Den Brand">Judith M A. 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Haagmans</name><affiliation><nlm:affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Segales, Joaquim" sort="Segales, Joaquim" uniqKey="Segales J" first="Joaquim" last="Segalés">Joaquim Segalés</name><affiliation><nlm:affiliation>IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Vergara Alert, Julia" sort="Vergara Alert, Julia" uniqKey="Vergara Alert J" first="Julia" last="Vergara-Alert">Julia Vergara-Alert</name><affiliation><nlm:affiliation>IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Bensaid, Albert" sort="Bensaid, Albert" uniqKey="Bensaid A" first="Albert" last="Bensaid">Albert Bensaid</name><affiliation><nlm:affiliation>IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Van Den Brand, Judith M A" sort="Van Den Brand, Judith M A" uniqKey="Van Den Brand J" first="Judith M A" last="Van Den Brand">Judith M A. Van Den Brand</name><affiliation><nlm:affiliation>Department of Pathobiology, Faculty of Veterinary Science, Utrecht University, 3512 JE, Utrecht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D M E" last="Osterhaus">Albert D M E. Osterhaus</name><affiliation><nlm:affiliation>Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Baumg Rtner, Wolfgang" sort="Baumg Rtner, Wolfgang" uniqKey="Baumg Rtner W" first="Wolfgang" last="Baumg Rtner">Wolfgang Baumg Rtner</name><affiliation><nlm:affiliation>Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany. Wolfgang.Baumgaertner@tiho-hannover.de.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Camelus</term><term>Cells, Cultured</term><term>Coronavirus Infections (metabolism)</term><term>Dipeptidyl Peptidase 4 (metabolism)</term><term>Fluorescent Antibody Technique</term><term>Immunohistochemistry</term><term>Keratin-14 (metabolism)</term><term>Keratin-18 (metabolism)</term><term>Keratin-4 (metabolism)</term><term>Keratin-5 (metabolism)</term><term>Microscopy, Electron, Scanning</term><term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term><term>Middle East Respiratory Syndrome Coronavirus (pathogenicity)</term><term>Middle East Respiratory Syndrome Coronavirus (ultrastructure)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dipeptidyl Peptidase 4</term><term>Keratin-14</term><term>Keratin-18</term><term>Keratin-4</term><term>Keratin-5</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Coronavirus Infections</term><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Camelus</term><term>Cells, Cultured</term><term>Fluorescent Antibody Technique</term><term>Immunohistochemistry</term><term>Microscopy, Electron, Scanning</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at day four post infection. Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14 expressing cells did not co-localize with virus. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary monocytes, but overall the expression level was lower in dromedaries. The present study underlines significant species-specific manifestations of MERS and highlights ciliary loss as an important finding in dromedaries. The obtained results promote a better understanding of coronavirus infections, which pose major health challenges.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29950581</PMID><DateCompleted><Year>2019</Year><Month>10</Month><Day>10</Day></DateCompleted><DateRevised><Year>2019</Year><Month>10</Month><Day>10</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><Issue>1</Issue><PubDate><Year>2018</Year><Month>06</Month><Day>27</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4.</ArticleTitle><Pagination><MedlinePgn>9778</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41598-018-28109-2</ELocationID><Abstract><AbstractText>Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at day four post infection. Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14 expressing cells did not co-localize with virus. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary monocytes, but overall the expression level was lower in dromedaries. The present study underlines significant species-specific manifestations of MERS and highlights ciliary loss as an important finding in dromedaries. The obtained results promote a better understanding of coronavirus infections, which pose major health challenges.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Haverkamp</LastName><ForeName>Ann-Kathrin</ForeName><Initials>AK</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lehmbecker</LastName><ForeName>Annika</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center for Systems Neuroscience, 30559, Hannover, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Spitzbarth</LastName><ForeName>Ingo</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center for Systems Neuroscience, 30559, Hannover, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Widagdo</LastName><ForeName>Widagdo</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haagmans</LastName><ForeName>Bart L</ForeName><Initials>BL</Initials><AffiliationInfo><Affiliation>Department of Viroscience, Erasmus Medical Center, 3015 CN, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Segalés</LastName><ForeName>Joaquim</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, UAB, 08193, Bellaterra, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vergara-Alert</LastName><ForeName>Julia</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bensaid</LastName><ForeName>Albert</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van den Brand</LastName><ForeName>Judith M A</ForeName><Initials>JMA</Initials><AffiliationInfo><Affiliation>Department of Pathobiology, Faculty of Veterinary Science, Utrecht University, 3512 JE, Utrecht, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Osterhaus</LastName><ForeName>Albert D M E</ForeName><Initials>ADME</Initials><AffiliationInfo><Affiliation>Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baumgärtner</LastName><ForeName>Wolfgang</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559, Hannover, Germany. Wolfgang.Baumgaertner@tiho-hannover.de.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center for Systems Neuroscience, 30559, Hannover, Germany. Wolfgang.Baumgaertner@tiho-hannover.de.</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></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>06</Month><Day>27</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci Rep</MedlineTA><NlmUniqueID>101563288</NlmUniqueID><ISSNLinking>2045-2322</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053547">Keratin-14</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053538">Keratin-18</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053527">Keratin-4</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D053555">Keratin-5</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.14.5</RegistryNumber><NameOfSubstance UI="D018819">Dipeptidyl Peptidase 4</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002162" MajorTopicYN="N">Camelus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018819" MajorTopicYN="N">Dipeptidyl Peptidase 4</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005455" MajorTopicYN="N">Fluorescent Antibody Technique</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D053547" MajorTopicYN="N">Keratin-14</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053538" MajorTopicYN="N">Keratin-18</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053527" MajorTopicYN="N">Keratin-4</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053555" MajorTopicYN="N">Keratin-5</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008855" MajorTopicYN="N">Microscopy, Electron, Scanning</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065207" 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