Date of Award:

12-2017

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Animal, Dairy, and Veterinary Sciences

Committee Chair(s)

E. Bart Tarbet

Committee

E. Bart Tarbet

Committee

Craig W. Day

Committee

Kerry A. Rood

Abstract

Enterovirus D68 (EV-D68) virus has become more prevalent over the last 15 to 20 years. EV-D68 attacks the respiratory system and can cause severe disease in individuals who have underlying respiratory problems. There have also been reports of individuals with EV-D68 showing signs of neurological system problems and acute flaccid paralysis. Because of the increase in patients with EV-D68 and also the potential for neurological disease, an animal model is needed to study the disease and to evaluate experimental therapies for EV-D68 infection.

To develop the animal model, 4-week old AG129 mice that lack alpha and beta interferon receptors, making them immunosuppressed, were used. The mice were infected with EV-D68 by the intranasal route to allow infection of the lungs. On day-3 post-infection the mice were euthanized and lungs were removed and homogenized for collection of virus. The newly collected virus was then used to infect another set of mice. This procedure was repeated 30 times. As passage number increased so did the amount of virus that was collected from the lungs of mice. The virus titer increased 320-fold between mouse passage 0 to 30.

At the end of the thirtieth passage, multiple tissues (lungs, liver, kidney, spleen, blood, brain, spinal cord and leg muscle) were collected from infected mice over several days and titered to demonstrate how quickly the virus spread to various tissues within the mouse. The virus replicated most rapidly in the lungs and remained in the lungs longer than the other tissues evaluated. However, large quantities of virus were found in all tissues evaluated.

Finally, several experimental antiviral compounds were evaluated: rupintrivir, pleconaril, ribavirin, enviroxime and guanidine, all of which showed therapeutic potential in cell culture. In the animal model rupintrivir, pleconaril, ribavirin and enviroxime did not show any therapeutic effect. Only guanidine reduced the amount of virus that was found in the lungs as well as in whole blood.

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