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Updated: May 2, 2026
A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
Rapid generation of a mouse model for Middle East respiratory syndrome
Jincun Zhao1, Kun Li, Christine Wohlford-Lenane
1Departments of Microbiology and Pediatrics, University of Iowa, Iowa City, IA 52240.
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.
Insights
Researchers developed a new mouse model for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. This MERS-CoV mouse model is crucial for developing effective vaccines and antiviral therapies against emerging zoonotic viruses.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Emerging zoonotic viruses like MERS-CoV pose significant public health threats.
- Rapid development of animal models is critical for preparedness against novel viral infections.
- No established small-animal model currently exists for MERS-CoV, hindering research.
Purpose of the Study:
- To develop and characterize a small-animal model for MERS-CoV infection.
- To evaluate potential therapeutic interventions and vaccines using the developed model.
- To investigate the host immune response to MERS-CoV infection.
Main Methods:
- Mice were sensitized to MERS-CoV by adenoviral vector transduction expressing the human receptor DPP4.
- Infection outcomes were assessed, including pneumonia development, inflammatory responses, and viral clearance.
- The role of type-I IFN signaling and T-cell responses in MERS-CoV infection was investigated.
- Efficacy of poly I:C therapy and a MERS-CoV spike protein vaccine (VEEV-RP) was evaluated.
Main Results:
- Adenoviral vector-mediated expression of human DPP4 sensitized mice to MERS-CoV, leading to pneumonia.
- Absence of type-I IFN signaling exacerbated disease severity.
- T-cell response was essential for viral clearance.
- The developed mouse model demonstrated efficacy of poly I:C and the VEEV-RP vaccine.
- Limited cross-protective immunity was observed between MERS-CoV and SARS-CoV.
Conclusions:
- A novel MERS-CoV mouse model susceptible to infection via human receptor expression has been established.
- This model is valuable for studying MERS-CoV pathogenesis and for evaluating antiviral therapies and vaccines.
- The findings support the rapid development of animal models for emerging respiratory viruses.
- Understanding host-pathogen interactions, including the role of IFN and T-cells, is crucial for MERS-CoV control.
