Date of Award

Fall 2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

Committee Chairperson

Ben Chambers, Ph.D.

Committee Member

Jessica Sowa, Ph.D.

Committee Member

Michael Rosario, Ph.D.

Abstract

Influenza A virus (IAV) is a highly infectious pathogen responsible for causing severe respiratory illness and death in humans and animals worldwide. Due to highly effective strategies to negate host antiviral defenses, IAV leads to the death of nearly all infected cells. Furthermore, IAV induces high levels of genome-damaging oxidative stress within infected cells and suppresses the cellular mismatch repair (MMR) mechanism, thereby inhibiting expression of key antiviral genes, which further contributes to cell death. However, recent studies have demonstrated that a subset of respiratory epithelial cells, called club cells, are able to non-lytically clear IAV and continue to survive following direct infection. These cells are able to maintain genome integrity during IAV infection using MMR activity, thus allowing for sufficient expression of antiviral genes. We hypothesize that several of these antiviral genes are critical to the non-lytic clearance of IAV, particularly HERC5 and OSAL. Through siRNA gene knockdown techniques, we have evaluated the impact of these genes on the non-lytic clearance mechanism of IAV-infected club cells.

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