Date of Award

2026

Embargo Period

4-17-2026

Document Type

Thesis

Degree Name

Master of Biomedical Science

Department

Cell and Molecular Biology and Pathobiology

College

College of Graduate Studies

First Advisor

Michael Bouchard

Abstract

Chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma worldwide. Despite the availability of a preventative vaccine, there are approximately 254 million people living with a chronic HBV infection. There are 9 known HBV genotypes, each with their own clinical impacts and manifestation in infected patients. HBx is the only regulatory protein encoded by the HBV genome and is required for efficient viral replication. HBx has many effects in infected hepatocytes besides known effects on HBV replication, such as localization to the mitochondria. HBx is also known to have impacts on mitochondrial membrane potential, mitochondrial permeability transition pore activity, and mitochondrial calcium homeostasis. Specifically, HBx is known to localize to the outer mitochondrial membrane (OMM) and interact with voltage dependent anion channel 3 (VDAC3). There are three isoforms of VDAC expressed by human cells: VDAC1, VDAC2, and VDAC3. There are various pathogens that utilize VDAC and mitochondrial biology to benefit their own life cycle or survival. In our studies, we aimed to understand the impact that VDAC isoform expression had on HBV replication and HBx localization. We utilized HepG2 cell lines that only expressed one isoform of VDAC and measured HBV replication and HBx localization to mitochondria. We found that HBV genotypes had differential replication depending on the VDAC isoform present. Cells with only VDAC1 expression showed drastically increased replication, while cells with only VDAC2 or VDAC3 showed lower viral replication across most genotypes tested. Additionally, HBx was found to localize to both VDAC1 and VDAC3, but not VDAC2. These studies uncover more about the importance of not only knowing which proteins HBx may interact with in cells, but also the impact on the virus because of the interaction. The new interaction of HBx-VDAC1 and the increased replication with only VDAC1 expression opens new avenues to therapies for HBV infected individuals and deepens the understanding of HBV biology.

Rights

Copyright is held by the author. All rights reserved.

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