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-...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/51deb0a819be41de97eecf54819fbc13
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spelling	oai:doaj.org-article:51deb0a819be41de97eecf54819fbc132021-12-02T16:07:51ZA spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques10.1038/s41598-018-28900-12045-2322https://doaj.org/article/51deb0a819be41de97eecf54819fbc132018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28900-1https://doaj.org/toc/2045-2322Abstract 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.Adam S. CockrellJoshua C. JohnsonIan N. MooreDavid X. LiuKevin W. BockMadeline G. DouglasRachel L. GrahamJeffrey SolomonLisa TorzewskiChristopher BartosRandy HartRalph S. BaricReed F. JohnsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	spike-modified middle east respiratory syndrome coronavirus (mers-cov) infectious clone elicits mild respiratory disease in infected rhesus macaques
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/51deb0a819be41de97eecf54819fbc13
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A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques

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