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

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  • Cockrell, Adam S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Johnson, Joshua C.
    • Other Affiliation: National Institutes of Health
  • Moore, Ian N.
    • Other Affiliation: National Institutes of Health
  • Liu, David X.
    • Other Affiliation: National Institutes of Health
  • Bock, Kevin W.
    • Other Affiliation: National Institutes of Health
  • Douglas, Madeline G.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Graham, Rachel L.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Solomon, Jeffrey
    • Other Affiliation: Frederick National Laboratory for Cancer Research
  • Torzewski, Lisa
    • Other Affiliation: National Institutes of Health
  • Bartos, Christopher
    • Other Affiliation: National Institutes of Health
  • Hart, Randy
    • Other Affiliation: National Institutes of Health
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Johnson, Reed F.
    • Other Affiliation: National Institutes of Health
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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  • Article
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  • In Copyright
Journal title
  • Scientific Reports
Journal volume
  • 8
Journal issue
  • 1
Language
  • English
ISSN
  • 2045-2322

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