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.

• Authors: Jincun Zhao, Kun Li, Christine Wohlford-Lenane, Sudhakar S Agnihothram, Craig Fett, Jingxian Zhao, Michael J Gale Jr, Ralph S Baric, Luis Enjuanes, Tom Gallagher, Paul B McCray Jr, Stanley Perlman
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 13 Pg. 4970-5 (Apr 01 2014) ISSN: 1091-6490 [Electronic] United States
• PMID: 24599590 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Viral
• Interferon Type I

Topics

• Animals
• Antibodies, Viral (immunology)
• CD8-Positive T-Lymphocytes (virology)
• Coronavirus (immunology, physiology)
• Coronavirus Infections (immunology, prevention & control, virology)
• Cross Reactions (immunology)
• Disease Models, Animal
• Humans
• Interferon Type I (metabolism)
• Mice
• Mice, Inbred C57BL
• Middle East
• Respiratory Tract Infections (immunology, prevention & control, virology)
• Severe Acute Respiratory Syndrome (immunology)
• Signal Transduction (immunology)