Date of Award

Summer 8-16-2024

Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

Advisor

Benjamin L. King

Second Committee Member

Melody N. Neely

Third Committee Member

Deborah Bouchard

Additional Committee Members

Clarissa Henry

Joshua Kelley

Abstract

Influenza causes 9-41 million illnesses yearly in the U.S. Our research explores innate immune responses to the virus, leveraging zebrafish larvae as models due to their immature adaptive immunity. We developed the Color-flu model, allowing real-time visualization of IAV infections and immune responses. Neutrophils, crucial for innate immunity, exhibit complex roles in antiviral responses; infection triggers inflammation and reactive oxygen species (ROS) production, which can lead to hyperinflammation if dysregulated. We hypothesize that optimizing neutrophil ROS can enhance IAV clearance while minimizing tissue damage. Our study uses genetic and pharmacological methods to assess the effects on survival, viral burden, and neutrophil behavior. Chapter 2 reviews IAV, ROS, and zebrafish models. Chapter 3 introduces Color-flu, enabling in vivo drug influence studies. Chapter 4 examines neutrophils' dual roles, finding that altering their levels is harmful. Chapter 5 focuses on ROS modulation, identifying it as key to managing hyperinflammation. Chapter 6 discusses future Color-flu projects and concludes the thesis.

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