Date of Award:

5-2019

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Animal, Dairy, and Veterinary Sciences

Department name when degree awarded

Animal, Dairy and Veterinary Science

Committee Chair(s)

E. Bart Tarbet

Committee

E. Bart Tarbet

Committee

Donald F. Smee

Committee

John D. Morrey

Committee

Jeffery O. Hall

Committee

Zhongde Wang

Committee

Nicholas E. Dickenson

Abstract

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.

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Dairy Science Commons

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