Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between M...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2020.1713705 |
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| author | Hannah Kleine-Weber Simon Schroeder Nadine Krüger Alexander Prokscha Hassan Y. Naim Marcel A. Müller Christian Drosten Stefan Pöhlmann Markus Hoffmann |
| author_facet | Hannah Kleine-Weber Simon Schroeder Nadine Krüger Alexander Prokscha Hassan Y. Naim Marcel A. Müller Christian Drosten Stefan Pöhlmann Markus Hoffmann |
| author_sort | Hannah Kleine-Weber |
| collection | DOAJ |
| description | Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients. |
| format | Article |
| id | doaj-art-6c0d81b7e961460e8a7dc357695bbdf0 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-6c0d81b7e961460e8a7dc357695bbdf02025-08-20T02:12:15ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-019115516810.1080/22221751.2020.1713705Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirusHannah Kleine-Weber0Simon Schroeder1Nadine Krüger2Alexander Prokscha3Hassan Y. Naim4Marcel A. Müller5Christian Drosten6Stefan Pöhlmann7Markus Hoffmann8Infection Biology Unit, German Primate Center, Göttingen, GermanyCharité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, GermanyInstitute of Virology, University of Veterinary Medicine Hannover, Hannover, GermanyDepartment of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, GermanyDepartment of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, GermanyCharité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, GermanyCharité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, GermanyInfection Biology Unit, German Primate Center, Göttingen, GermanyInfection Biology Unit, German Primate Center, Göttingen, GermanyMiddle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.https://www.tandfonline.com/doi/10.1080/22221751.2020.1713705Middle East respiratory syndrome coronavirusspike glycoproteindipeptidyl peptidase 4polymorphismsreceptor binding |
| spellingShingle | Hannah Kleine-Weber Simon Schroeder Nadine Krüger Alexander Prokscha Hassan Y. Naim Marcel A. Müller Christian Drosten Stefan Pöhlmann Markus Hoffmann Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus Emerging Microbes and Infections Middle East respiratory syndrome coronavirus spike glycoprotein dipeptidyl peptidase 4 polymorphisms receptor binding |
| title | Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus |
| title_full | Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus |
| title_fullStr | Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus |
| title_full_unstemmed | Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus |
| title_short | Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus |
| title_sort | polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of middle east respiratory syndrome coronavirus |
| topic | Middle East respiratory syndrome coronavirus spike glycoprotein dipeptidyl peptidase 4 polymorphisms receptor binding |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2020.1713705 |
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