A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques

• Published in: Scientific reports 2018-07, Vol.8 (1), p.10727-9, Article 10727
• Main Authors: Cockrell, Adam S., Johnson, Joshua C., Moore, Ian N., Liu, David X., Bock, Kevin W., Douglas, Madeline G., Graham, Rachel L., Solomon, Jeffrey, Torzewski, Lisa, Bartos, Christopher, Hart, Randy, Baric, Ralph S., Johnson, Reed F.
• Format: Article
• Language: English
• Subjects: 13/106; 14/63; 631/326/421; 631/326/596/2555; 64; Animal models; Animals; Computed tomography; Coronaviridae; Coronavirus Infections - diagnosis; Coronavirus Infections - pathology; Coronavirus Infections - virology; Coronaviruses; Disease Models, Animal; Humanities and Social Sciences; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Lung - diagnostic imaging; Lung - pathology; Lung - virology; Lung diseases; Macaca mulatta; Middle East Respiratory Syndrome Coronavirus - genetics; Middle East Respiratory Syndrome Coronavirus - isolation & purification; Middle East Respiratory Syndrome Coronavirus - pathogenicity; Middle East Respiratory Syndrome Coronavirus - physiology; multidisciplinary; Primates; Respiratory diseases; Respiratory tract; RNA, Viral - isolation & purification; Science; Science (multidisciplinary); Severity of Illness Index; Tomography, X-Ray Computed; Viral Load - genetics; Virus Replication - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-28900-1

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.