Phenotypic and genetic characterization of MERS coronaviruses from Africa to understand their zoonotic potential
Copyright © 2021 the Author(s). Published by PNAS..
Coronaviruses are pathogens of pandemic potential. Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. More than 70% of MERS-CoV-infected dromedaries are found in East, North, and West Africa, but zoonotic MERS disease is only reported from the Arabian Peninsula. We compared viral replication competence of clade A and B viruses from the Arabian Peninsula with genetically diverse clade C viruses found in East (Egypt, Kenya, and Ethiopia), North (Morocco), and West (Nigeria and Burkina Faso) Africa. Viruses from Africa had lower replication competence in ex vivo cultures of the human lung and in lungs of experimentally infected human-DPP4 (hDPP4) knockin mice. We used lentivirus pseudotypes expressing MERS-CoV spike from Saudi Arabian clade A prototype strain (EMC) or African clade C1.1 viruses and demonstrated that clade C1.1 spike was associated with reduced virus entry into the respiratory epithelial cell line Calu-3. Isogenic EMC viruses with spike protein from EMC or clade C1.1 generated by reverse genetics showed that the clade C1.1 spike was associated with reduced virus replication competence in Calu-3 cells in vitro, in ex vivo human bronchus, and in lungs of hDPP4 knockin mice in vivo. These findings may explain why zoonotic MERS disease has not been reported from Africa so far, despite exposure to and infection with MERS-CoV.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:118 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 118(2021), 25 vom: 22. Juni |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Ziqi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.06.2021 Date Revised 05.07.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2103984118 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM326477594 |
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| 245 | 1 | 0 | |a Phenotypic and genetic characterization of MERS coronaviruses from Africa to understand their zoonotic potential |
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| 500 | |a Date Revised 05.07.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 the Author(s). Published by PNAS. | ||
| 520 | |a Coronaviruses are pathogens of pandemic potential. Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. More than 70% of MERS-CoV-infected dromedaries are found in East, North, and West Africa, but zoonotic MERS disease is only reported from the Arabian Peninsula. We compared viral replication competence of clade A and B viruses from the Arabian Peninsula with genetically diverse clade C viruses found in East (Egypt, Kenya, and Ethiopia), North (Morocco), and West (Nigeria and Burkina Faso) Africa. Viruses from Africa had lower replication competence in ex vivo cultures of the human lung and in lungs of experimentally infected human-DPP4 (hDPP4) knockin mice. We used lentivirus pseudotypes expressing MERS-CoV spike from Saudi Arabian clade A prototype strain (EMC) or African clade C1.1 viruses and demonstrated that clade C1.1 spike was associated with reduced virus entry into the respiratory epithelial cell line Calu-3. Isogenic EMC viruses with spike protein from EMC or clade C1.1 generated by reverse genetics showed that the clade C1.1 spike was associated with reduced virus replication competence in Calu-3 cells in vitro, in ex vivo human bronchus, and in lungs of hDPP4 knockin mice in vivo. These findings may explain why zoonotic MERS disease has not been reported from Africa so far, despite exposure to and infection with MERS-CoV | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 700 | 1 | |a El Masry, Ihab |e verfasserin |4 aut | |
| 700 | 1 | |a Von Dobschuetz, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Kalpravidh, Wantanee |e verfasserin |4 aut | |
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| 700 | 1 | |a Fassi-Fihri, Ouafaa |e verfasserin |4 aut | |
| 700 | 1 | |a Trarore, Amadou |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Weiwen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yanqun |e verfasserin |4 aut | |
| 700 | 1 | |a Nicholls, John M |e verfasserin |4 aut | |
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| 700 | 1 | |a Chan, Michael C W |e verfasserin |4 aut | |
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