Date of Award:

5-2026

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Veterinary Clinical and Life Science Department

Committee Chair(s)

E. Bart Tarbet

Committee

E. Bart Tarbet

Committee

Brett L. Hurst

Committee

Carmen King

Abstract

Each year, the influenza virus is responsible for hundreds of thousands of deaths. The virus has an RNA genome comprised of eight segments. The genome of the virus evolves through mutations and reassortment. Continuous evolution makes influenza virus a significant threat to public health. 

Antiviral therapies such as oseltamivir (Tamiflu®) and baloxavir marboxil (Xofluza®) are currently FDA-approved to treat influenza virus infections. These antivirals function to limit the severity of the symptoms common with an influenza virus infection by inhibiting the viral replication cycle. However, antiviral therapies do not limit the intensity of the host immune response. 

In 2006, Dr. David Fedson proposed a hypothesis about combining an antiviral and immunomodulator in a combination therapy to control the intensity of the host immune response during an influenza A virus infection. We evaluated JAK-STAT inhibitors as the immunomodulator in a combination therapy with oseltamivir. JAK-STAT inhibitors are drugs that limit the cytokines that induce a host immune response. While not suited for long term use, these inhibitors have potential anti-inflammatory properties. When oseltamivir and oclacitinib, a JAK-STAT inhibitor, were combined to treat BALB/c mice challenged with a lethal dose of influenza A/CA/04/09 (H1N1pdm) virus, an improvement of survival was observed.

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