Dysregulation of Complement Factor H During Dengue Virus Infection in vitro

Author: Joshua Dubowsky

Dubowsky, Joshua, 2023 Dysregulation of Complement Factor H During Dengue Virus Infection in vitro, Flinders University, College of Medicine and Public Health

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Dengue Virus (DENV) infects over 390 million people annually, causing debilitating and potentially life threatening disease. Yet, there is currently no approved antiviral to treat dengue and only one vaccine with limitations on its utility. Severe dengue can be fatal, and is caused by an exaggerated inflammatory response, driven partially by dysregulated complement activation, which correlates with poorer patient outcome. Previously, our laboratory has demonstrated in vitro that excessive complement alternative pathway (AP) activation in response to DENV results from increased factor B (FB), despite induction of mRNA for the AP regulator factor H (FH). Therefore, this project aimed to define the stimuli of FH induction, quantitated FH mRNA and protein and characterised FH-ligands and FH-cell localisation in response to DENV infection.

Keywords: Dengue Virus, DENV, Complement, Factor H, CFH, FHL-1, Factor H Related, CFHR3-1, sialic acid, glycosaminoglycans

Subject: Medical Science thesis

Thesis type: Doctor of Philosophy
Completed: 2023
School: College of Medicine and Public Health
Supervisor: Professor Jillian Carr