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Thesis
The effect of the hepatitis B virus HBx interacting protein, HBXIP, on HBV replication
Master of Science (M.S.), Drexel University
Apr 2022
DOI:
https://doi.org/10.17918/00001189
Abstract
Liver cancer is the second leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) accounts for 70-90% of all liver cancers. Globally 50% of HCC cases are caused by a chronic hepatitis B virus (HBV) infection. Despite the availability of a preventative vaccine, worldwide, approximately 296 million people have a chronic HBV infection. Current therapies, while effective, are not curative because they do not target the replicative intermediate of HBV, covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is a non-structural, multifunctional, regulatory encode by the HBV genome. HBx expression is necessary for HBV replication and influences the development of HBV-associated HCC. HBx also modulates several host cell signaling pathways. We previously showed that HBx activates the mechanistic target of rapamycin complex 1 (mTORC1), which surprisingly, diminishes HBV replication. In 1998, a host protein, then named HBX-interacting protein (HBXIP), was identified as a cellular factor that interacts with HBx and decreases HBV replication. Interestingly, in 2012, HBXIP was shown to be a major component of a complex that activates mTORC1 signaling. We hypothesized that the interaction of HBx and HBXIP may be linked to HBx activation of mTORC1 and the associated decrease in HBV replication. Here, we report the results of studies that demonstrate that activation of mTORC1 via overexpression of HBXIP decreased the expression of the HBV capsid protein that is necessary for HBV replication. This effect was partially rescued when mTORC1 activation was inhibited in cells with overexpressed HBXIP. These studies provide evidence that inhibition of HBV replication via HBx activation of mTORC1 may be mediated by HBXIP
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Details
- Title
- The effect of the hepatitis B virus HBx interacting protein, HBXIP, on HBV replication
- Creators
- Aditi Hemant Shimpi
- Contributors
- Michael Bouchard (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- ix, 99 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Medicine (Graduate); College of Medicine; Hematology and Oncology; Drexel University
- Other Identifier
- 991018021231104721