Journal article
Rapid generation of a mouse model for Middle East respiratory syndrome
Proceedings of the National Academy of Sciences of the United States of America, Vol.111(13), pp.4970-4975
04/01/2014
DOI: 10.1073/pnas.1323279111
PMCID: PMC3977243
PMID: 24599590
Abstract
In this era of continued emergence of zoonotic virus infections, the rapid development of rodent models represents a critical barrier to public health preparedness, including the testing of antivirus therapy and vaccines. The Middle East respiratory syndrome coronavirus (MERS-CoV) was recently identified as the causative agent of a severe pneumonia. Given the ability of coronavirus to rapidly adapt to new hosts, a major public health concern is that MERS-CoV will further adapt to replication in humans, triggering a pandemic. No small-animal model for this infection is currently available, but studies suggest that virus entry factors can confer virus susceptibility. Here, we show that mice were sensitized to MERS-CoV infection by prior transduction with adenoviral vectors expressing the human host-cell receptor dipeptidyl peptidase 4. Mice developed a pneumonia characterized by extensive inflammatory-cell infiltration with virus clearance occurring 6-8 d after infection. Clinical disease and histopathological changes were more severe in the absence of type-I IFN signaling whereas the T-cell response was required for virus clearance. Using these mice, we demonstrated the efficacy of a therapeutic intervention (poly I:C) and a potential vaccine [Venezuelan equine encephalitis replicon particles expressing MERS-CoV spike protein]. We also found little protective cross-reactivity between MERS-CoV and the severe acute respiratory syndrome-CoV. Our results demonstrate that this system will be useful for MERS-CoV studies and for the rapid development of relevant animal models for emerging respiratory viral infections.
Details
- Title: Subtitle
- Rapid generation of a mouse model for Middle East respiratory syndrome
- Creators
- Jincun Zhao - University of IowaKun LiChristine Wohlford-LenaneSudhakar S AgnihothramCraig FettJingxian ZhaoMichael J Gale JrRalph S BaricLuis EnjuanesTom GallagherPaul B McCray JrStanley Perlman
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences of the United States of America, Vol.111(13), pp.4970-4975
- DOI
- 10.1073/pnas.1323279111
- PMID
- 24599590
- PMCID
- PMC3977243
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- United States
- Grant note
- P30 ES005605 / NIEHS NIH HHS AI057157 / NIAID NIH HHS R01AI091322 / NIAID NIH HHS U54 AI057157 / NIAID NIH HHS P0106099 / PHS HHS AI083019 / NIAID NIH HHS AI074973 / NIAID NIH HHS R01 AI091322 / NIAID NIH HHS P01 AI060699 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS R01 AI074973 / NIAID NIH HHS U19 AI083019 / NIAID NIH HHS
- Language
- English
- Date published
- 04/01/2014
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9983777352302771
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