Generation of a transgenic mouse model of middle east respiratory syndrome coronavirus infection and disease

Anurodh Shankar Agrawal, Tania Garron, Xinrong Tao, Bihung Peng, Maki Wakamiya, Teh Sheng Chan, Robert B. Couch, Chien-Te Tseng

Research output: Contribution to journalArticle

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Abstract

The emergence of Middle East respiratory syndrome-coronavirus (MERS-CoV) in the Middle East since 2012 has caused more than 900 human infections with ~40% mortality to date. Animal models are needed for studying pathogenesis and for development of preventive and therapeutic agents against MERS-CoV infection. Nonhuman primates (rhesus macaques and marmosets) are expensive models of limited availability. Although a mouse lung infection model has been described using adenovirus vectors expressing human CD26/dipeptidyl peptidase 4 (DPP4), it is believed that a transgenic mouse model is needed for MERSCoV research. We have developed this transgenic mouse model as indicated in this study. We show that transgenic mice globally expressing hCD26/DPP4 were fully permissive to MERS-CoV infection, resulting in relentless weight loss and death within days postinfection. High infectious virus titers were recovered primarily from the lungs and brains of mice at 2 and 4 days postinfection, respectively, whereas viral RNAs were also detected in the heart, spleen, and intestine, indicating a disseminating viral infection. Infected Tg+ mice developed a progressive pneumonia, characterized by extensive inflammatory infiltration. In contrast, an inconsistent mild perivascular cuffing was the only pathological change associated with the infected brains. Moreover, infected Tg+ mice were able to activate genes encoding for many antiviral and inflammatory mediators within the lungs and brains, coinciding with the high levels of viral replication. This new and unique transgenic mouse model will be useful for furthering knowledge of MERS pathogenesis and for the development of vaccine and treatments against MERS-CoV infection.

Original languageEnglish (US)
Pages (from-to)3659-3670
Number of pages12
JournalJournal of Virology
Volume89
Issue number7
DOIs
StatePublished - 2015

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Coronavirus Infections
Transgenic Mice
animal models
genetically modified organisms
Dipeptidyl Peptidase 4
infection
Lung
mice
Brain
peptidases
lungs
brain
Callithrix
Middle East
Viral RNA
Virus Diseases
pathogenesis
Infection
Macaca mulatta
Viral Load

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Generation of a transgenic mouse model of middle east respiratory syndrome coronavirus infection and disease. / Agrawal, Anurodh Shankar; Garron, Tania; Tao, Xinrong; Peng, Bihung; Wakamiya, Maki; Chan, Teh Sheng; Couch, Robert B.; Tseng, Chien-Te.

In: Journal of Virology, Vol. 89, No. 7, 2015, p. 3659-3670.

Research output: Contribution to journalArticle

Agrawal, Anurodh Shankar ; Garron, Tania ; Tao, Xinrong ; Peng, Bihung ; Wakamiya, Maki ; Chan, Teh Sheng ; Couch, Robert B. ; Tseng, Chien-Te. / Generation of a transgenic mouse model of middle east respiratory syndrome coronavirus infection and disease. In: Journal of Virology. 2015 ; Vol. 89, No. 7. pp. 3659-3670.
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