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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Maporal Hantavirus Causes Mild Pathology in Deer Mice (Peromyscus maniculatus)
Amanda McGuire1, Kaitlyn Miedema2, Joseph R Fauver3
1Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. amanda.mcguire@colostate.edu.
Abstract:
Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the deer mouse (Peromyscus maniculatus), the natural reservoir host of Sin Nombre virus (SNV), and a virus that is pathogenic in another animal model to examine immune response of a reservoir host species. Deer mice were inoculated with MAPV, and viral RNA was detected in several organs of all deer mice during the 56 day experiment. Infected animals generated both nucleocapsid-specific and neutralizing antibodies. Histopathological lesions were minimal to mild with the peak of the lesions detected at 7-14 days postinfection, mainly in the lungs, heart, and liver. Low to modest levels of cytokine gene expression were detected in spleens and lungs of infected deer mice, and deer mouse primary pulmonary cells generated with endothelial cell growth factors were susceptible to MAPV with viral RNA accumulating in the cellular fraction compared to infected Vero cells. Most features resembled that of SNV infection of deer mice, suggesting this model may be an ABSL-3 surrogate for studying the host response of a New World hantavirus reservoir.
Insights
A new animal model using Maporal virus (MAPV) in deer mice under ABSL-3 conditions allows studying hantavirus reservoir host responses. This model mimics Sin Nombre virus (SNV) infection, aiding research into New World hantaviruses.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Rodent-borne hantaviruses cause severe human diseases like HCPS and HFRS.
- High-level containment (ABSL-4) for HCPS-causing viruses limits reservoir host interaction research.
- Maporal virus (MAPV), a South American hantavirus, is not pathogenic in humans, allowing ABSL-3 research.
Purpose of the Study:
- To develop an ABSL-3 hantavirus infection model using deer mice (Peromyscus maniculatus).
- To examine the immune response of a reservoir host species to a New World hantavirus.
- To use MAPV in deer mice as a surrogate for studying Sin Nombre virus (SNV) host responses.
Main Methods:
- Deer mice were inoculated with MAPV and monitored for 56 days.
- Viral RNA detection, antibody analysis (nucleocapsid-specific and neutralizing), and histopathology were performed.
- Cytokine gene expression and MAPV susceptibility in primary pulmonary cells were assessed.
Main Results:
- MAPV RNA was detected in multiple organs of infected deer mice.
- Infected deer mice produced nucleocapsid-specific and neutralizing antibodies.
- Minimal to mild lesions were observed primarily in lungs, heart, and liver; cytokine expression was low to modest.
Conclusions:
- The MAPV-infected deer mouse model replicates key features of SNV infection in a reservoir host.
- This ABSL-3 model provides a viable alternative for studying New World hantavirus reservoir host responses.
- The model facilitates research into hantavirus-host interactions without requiring ABSL-4 containment.

