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A mouse model for MERS coronavirus-induced acute respiratory distress syndrome

Open access
Cockrell, Adam S., Yount, Boyd L., Scobey, Trevor, Jensen, Kara, Douglas, Madeline, Beall, Anne, Tang, Xian-Chun, Marasco, Wayne A., Heise, Mark T., Baric, Ralph S.·2016·Nature Microbiology

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR–Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.

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Metadata

Authors
Cockrell, A. S., Yount, B. L., Scobey, T., Jensen, K., Douglas, M., Beall, A., Tang, X.-C., Marasco, W. A., Heise, M. T., & Baric, R. S.
Venue
Nature Microbiology
Published
2016-11-28
Volume
2
Issue
2
Pages
16226-16226
ISSN
2058-5276 (ISSN-L)
OpenAlex
W2559337285
Cited by
206
References
4
FWCI
15.68
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: A mouse model for MERS coronavirus-induced acute respiratory distress syndrome. https://app.cochat.ai/papers/10.1038/nmicrobiol.2016.226
The paper
Cockrell, A. S., Yount, B. L., Scobey, T., Jensen, K., Douglas, M., Beall, A., Tang, X.-C., Marasco, W. A., Heise, M. T., & Baric, R. S. (2016). A mouse model for MERS coronavirus-induced acute respiratory distress syndrome. Nature Microbiology. https://doi.org/10.1038/nmicrobiol.2016.226

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