A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques
Abstract The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-28900-1 |
| _version_ | 1830288009756409856 |
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| author | Adam S. Cockrell Joshua C. Johnson Ian N. Moore David X. Liu Kevin W. Bock Madeline G. Douglas Rachel L. Graham Jeffrey Solomon Lisa Torzewski Christopher Bartos Randy Hart Ralph S. Baric Reed F. Johnson |
| author_facet | Adam S. Cockrell Joshua C. Johnson Ian N. Moore David X. Liu Kevin W. Bock Madeline G. Douglas Rachel L. Graham Jeffrey Solomon Lisa Torzewski Christopher Bartos Randy Hart Ralph S. Baric Reed F. Johnson |
| author_sort | Adam S. Cockrell |
| collection | DOAJ |
| description | Abstract The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. Considering this limitation, we wanted to ascertain the effectiveness of using a MERS-CoV infectious clone (icMERS-0) previously shown to replicate to higher titers than the wild-type EMC 2012 strain. We observed respiratory disease resulting from exposure to the icMERS-0 strain as measured by CT in rhesus monkeys with concomitant detection of virus antigen by immunohistochemistry. Overall, respiratory disease was mild and transient, resolving by day 30 post-infection. Although pulmonary disease was mild, these results demonstrate for the first time the utility of CT imaging to measure disease elicited by a MERS-CoV infectious clone system in nonhuman primate models. |
| first_indexed | 2024-12-19T04:28:05Z |
| format | Article |
| id | doaj.art-51deb0a819be41de97eecf54819fbc13 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:28:05Z |
| publishDate | 2018-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-51deb0a819be41de97eecf54819fbc132022-12-21T20:35:58ZengNature PortfolioScientific Reports2045-23222018-07-01811910.1038/s41598-018-28900-1A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaquesAdam S. Cockrell0Joshua C. Johnson1Ian N. Moore2David X. Liu3Kevin W. Bock4Madeline G. Douglas5Rachel L. Graham6Jeffrey Solomon7Lisa Torzewski8Christopher Bartos9Randy Hart10Ralph S. Baric11Reed F. Johnson12Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel HillIntegrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research PlazaInfectious Disease Pathogenesis Section, Comparative Medicine Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthIntegrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research PlazaInfectious Disease Pathogenesis Section, Comparative Medicine Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDepartment of Epidemiology, University of North Carolina-Chapel Hill, Chapel HillDepartment of Epidemiology, University of North Carolina-Chapel Hill, Chapel HillClinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer ResearchIntegrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research PlazaIntegrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research PlazaIntegrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research PlazaDepartment of Epidemiology, University of North Carolina-Chapel Hill, Chapel HillEmerging Viral Pathogens Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research PlazaAbstract The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. Considering this limitation, we wanted to ascertain the effectiveness of using a MERS-CoV infectious clone (icMERS-0) previously shown to replicate to higher titers than the wild-type EMC 2012 strain. We observed respiratory disease resulting from exposure to the icMERS-0 strain as measured by CT in rhesus monkeys with concomitant detection of virus antigen by immunohistochemistry. Overall, respiratory disease was mild and transient, resolving by day 30 post-infection. Although pulmonary disease was mild, these results demonstrate for the first time the utility of CT imaging to measure disease elicited by a MERS-CoV infectious clone system in nonhuman primate models.https://doi.org/10.1038/s41598-018-28900-1 |
| spellingShingle | Adam S. Cockrell Joshua C. Johnson Ian N. Moore David X. Liu Kevin W. Bock Madeline G. Douglas Rachel L. Graham Jeffrey Solomon Lisa Torzewski Christopher Bartos Randy Hart Ralph S. Baric Reed F. Johnson A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques Scientific Reports |
| title | A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques |
| title_full | A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques |
| title_fullStr | A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques |
| title_full_unstemmed | A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques |
| title_short | A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques |
| title_sort | spike modified middle east respiratory syndrome coronavirus mers cov infectious clone elicits mild respiratory disease in infected rhesus macaques |
| url | https://doi.org/10.1038/s41598-018-28900-1 |
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