Emma Boudreaux

Document Type

Honors Thesis

Major

Biochemistry

Advisor(s)

Benjamin L. King

Committee Members

Sally D. Molloy, Melissa Maginnis

Graduation Year

May, 2025

Publication Date

2025

Abstract

Infection with influenza A virus (IAV) caused over 350,000 mortalities between 2010 and 2023 within the United States despite high vaccination levels. A more thorough understanding of the host mechanisms used to combat IAV infection will enable the identification of potential targets in order to develop more effective antiviral therapies, preventing thousands of deaths annually. One of these host-cell mechanisms is the production of cytokines that initiate a robust immune response to combat viral infection, called interferons (IFNs). Zebrafish larvae have proven to be effective models in studying the innate immune response to IAV infections. In zebrafish, there are four type I interferon homologs, ifnphi1, ifnphi2, ifnphi3, and ifnphi4, that respond to virus infection and activate an immune response through a signaling cascade homologous to mammals. As in mammals, binding of interferon to its receptor in zebrafish activates interferon regulatory factors (IRFs) that drive the expression of dozens of interferon stimulated genes (ISGs). As only ifnphi1 has been shown to be activated in response to IAV infection in zebrafish, we seek to characterize the expression of all four IFNs along with IRFs and ISGs. To test our hypothesis that IFNs, IRFs and ISGs are upregulated in response to IAV infection in zebrafish, we used a combination of qPCR assays and analyses of RNA-Seq data of IAV- infected zebrafish from 0 to 72 hpi. Knowledge of the IFN response to IAV infection in our zebrafish model will help us evaluate small molecules that may enhance the antiviral response.

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