Development of Mouse Models for Respiratory and Neurological Disease Caused by Enterovirus D68 and Evaluation of Antiviral Therapies
Date of Award:
Doctor of Philosophy (PhD)
Animal, Dairy, and Veterinary Sciences
E. Bart Tarbet
E. Bart Tarbet
Donald F. Smee
John D. Morrey
Jeffery O. Hall
Nicholas E. Dickenson
Enterovirus D68 (EV-D68) is a virus that normally causes disease in children. While this virus typically causes a respiratory infection, in 2014, a large outbreak of the virus was associated with patients that had paralysis of the arms or legs. Even though the virus was discovered in 1962, little was known about the life cycle of the virus or its ability to cause disease. An animal model of disease was needed to understand how the virus causes disease and to develop antiviral compounds to target the virus life cycle.
We adapted the virus by serial-passage in lung tissues from mice deficient in interferon receptors. Using the adapted virus, we established a model of respiratory disease where the virus was able to replicate and cause moderate damage to the lung tissue. We created a separate model of disease where the virus caused paralysis and mortality in infected mice, similar to symptoms seen in infected children. Lastly, we evaluated several antiviral compounds to determine if they were able to protect the mice from virus replication and mortality. Guanidine was able to reduce the amount of virus in each tissue as well as protect mice from paralysis and mortality. In addition, human intravenous immunoglobulin (hIVIG), a mixture of pooled antibodies from human donors, did not reduce the amount of virus in the lungs, but did protect mice from paralysis and mortality.
Hurst, Brett L., "Development of Mouse Models for Respiratory and Neurological Disease Caused by Enterovirus D68 and Evaluation of Antiviral Therapies" (2019). All Graduate Theses and Dissertations. 7421.
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