Rapid generation of a mouse model for Middle East respiratory syndrome Journal Article

Authors: Zhao, J; Li, K.; Wohlford-Lenane, C.; Agnihothram, S. S.; Fett, C.; Gale, M. J., Jr; Baric, R. S.; Enjuanes, L.; Gallagher, T.; McCray, P. B., Jr; Perlman, S.
Article Title: Rapid generation of a mouse model for Middle East respiratory syndrome
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.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 111
Issue: 13
ISSN: 1091-6490; 0027-8424
Publisher: Unknown  
Journal Place: United States
Date Published: 2014
Start Page: 4970
End Page: 4975
Language: eng
Notes: LR: 20150423; GR: AI057157/AI/NIAID NIH HHS/United States; GR: AI074973/AI/NIAID NIH HHS/United States; GR: AI083019/AI/NIAID NIH HHS/United States; GR: P01 AI060699/AI/NIAID NIH HHS/United States; GR: P0106099/PHS HHS/United States; GR: P30 ES005605/ES/NIEHS NIH HHS/United States; GR: R01 AI091322/AI/NIAID NIH HHS/United States; GR: R01AI091322/AI/NIAID NIH HHS/United States; GR: U54 AI057157/AI/NIAID NIH HHS/United States; JID: 7505876; 0 (Antibodies, Viral); 0 (Interferon Type I); OID: NLM: PMC3977243; OTO: NOTNLM; 2014/03/05 [aheadofprint]; ppublish