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

经过刺突修饰的中东呼吸综合征冠状病毒 (MERS-CoV) 感染性克隆在受感染的恒河猴中引发轻微呼吸道疾病

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作者: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

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.

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