Infection with MERS-CoV causes lethal pneumonia in the common marmoset

The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of cou...

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Bibliographic Details
Published in:PLoS pathogens 2014-08, Vol.10 (8), p.e1004250-e1004250
Main Authors: Falzarano, Darryl, de Wit, Emmie, Feldmann, Friederike, Rasmussen, Angela L, Okumura, Atsushi, Peng, Xinxia, Thomas, Matthew J, van Doremalen, Neeltje, Haddock, Elaine, Nagy, Lee, LaCasse, Rachel, Liu, Tingting, Zhu, Jiang, McLellan, Jason S, Scott, Dana P, Katze, Michael G, Feldmann, Heinz, Munster, Vincent J
Format: Article
Language:English
Subjects:
Adenoviruses
Animal diseases
Animals
Bacterial pneumonia
Biology and life sciences
Blood
Callithrix
Causes of
Confidence intervals
Coronavirus Infections - pathology
Coronavirus Infections - virology
Disease Models, Animal
Gene expression
Hematology
Illnesses
Immunohistochemistry
Infections
Male
Middle East Respiratory Syndrome Coronavirus
Mortality
Pathogenesis
Pneumonia
Pneumonia, Viral - pathology
Pneumonia, Viral - virology
Proteins
Real-Time Polymerase Chain Reaction
Research and Analysis Methods
Respiratory diseases
Studies
Zoonoses
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Summary:The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia leading to euthanasia of some animals. Extensive lesions were evident in the lungs of all animals necropsied at different time points post inoculation. Some animals were also viremic; high viral loads were detected in the lungs of all infected animals, and total RNAseq demonstrated the induction of immune and inflammatory pathways. This is the first description of a severe, partially lethal, disease model of MERS-CoV, and as such will have a major impact on the ability to assess the efficacy of vaccines and treatment strategies as well as allowing more detailed pathogenesis studies.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1004250