Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Program Name/Specialization

Biological and Chemical Sciences

Faculty/School

Faculty of Science

First Advisor

Stephanie DeWitte-Orr

Advisor Role

Principal Investigator

Abstract

Aquaculture now outpaces traditional capture fisheries as the world population and demand for sustainable protein sources increases. Wild and farmed species are increasingly susceptible to pathogen spread as global temperatures rise and stocking densities increase. Despite the devastating losses experienced by aquaculture due to viral infections, there remain few effective prophylactic antiviral therapeutics. Long double-stranded (ds)RNA is a uniquely viral molecule produced by nearly all viruses during their replication cycle, and its detection by salmonids like rainbow trout (Oncorhynchus mykiss) and chinook salmon (Oncorhynchus tshawytsha) leads to the establishment of a defensive antiviral state. Previous in vitro studies demonstrated a reduction in the severity of viral infections following prophylactic treatment by long dsRNA delivered by nanoparticles). This dissertation determined that: i) the toxicity imparted by cationic stearylamine liposomes outweighed their protective capabilities in vitro, ii) phytoglycogen nanoparticles enhanced the antiviral protection of HMW poly I:C in vitro, iii) HMW poly I:C delivered by phytoglycogen nanoparticles enhanced peripheral blood leukocyte phagocytosis, antiviral gene expression, and metabolism ex vivo while also inducing antiviral gene expression in ex vivo intestine models, and iv) the loss of the cytosolic PRR MDA5 decreased the responsiveness of chinook salmon embryonic cells to dsRNA over 500bp and increased susceptibility to viral infection. Together, this foundational knowledge can direct further investigations into the potential of nanocarriers to enhance antiviral protection in vivo. to protect the growing aquaculture industry against significant losses from viral infections and inform disease management strategies in wild populations.

Convocation Year

2026

Convocation Season

Spring

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