Date of Award:

12-2023

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Animal, Dairy, and Veterinary Sciences

Committee Chair(s)

Brett L. Hurst

Committee

Brett L. Hurst

Committee

E. Bart Tarbet

Committee

Shawn M. Zimmerman

Abstract

Enterovirus D68 (EV-D68) is a virus that causes respiratory disease. Children are most commonly affected by EV-D68 but immunocompromised adults can also get infected and develop severe disease signs. In 2014, the United States experienced an unprecedented outbreak of EV-D68. Similar outbreaks were also observed in 2016, 2018 and 2022. Interestingly, few EV-D68 infections were observed in 2020, likely due to public health measures put in place to reduce the spread of another respiratory disease, coronavirus disease 2019 (COVID-19). EV-D68 is in the same virus family as polio, and one of the most concerning findings from these outbreaks is that EV-D68 cases were strongly correlated to cases of paralysis, typically in the upper limbs of infected children.

There are currently no recommended antiviral drugs or vaccines to fight EV-D68 infection. We evaluated six different antiviral compounds and determined their activity in cells against EV-D68. We found that Enviroxime, EIDD-1931, and NITD008 limited the ability of EV-D68 to replicate and cause cell death. We also characterized EV-D68 in a mouse model of infection to provide insights into the neurological disease caused by EV-D68. EV-D68 caused death and paralysis in 4-7-day old immunocompromised mice. Virus was detected in leg muscle, spinal cord, and lung tissues of infected mice. We evaluated EIDD-1931 and IVIg in our EV-D68 mouse model and found both treatments significantly reduced mortality mice. Treatment with IVIg was also able to significantly reduce paralysis in EV-D68-infected mice.

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