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Dissertation
Establishing a model of HIV infection in macrophages to assess HIV / HBV co-infection driven liver disease
Doctor of Philosophy (Ph.D.), Drexel University
Jul 2025
DOI:
https://doi.org/10.17918/00011134
Abstract
Safe and effective antiviral therapies (AT) have significantly improved outcomes for people with human immunodeficiency virus (HIV) (PWH) and people with hepatitis B virus (HBV). However, these treatments are not curative and individuals with either virus remain at increased risk for liver-related complications, such as hepatocellular carcinoma (HCC). Co-infection increases this risk, as PWH and HBV tend to develop HCC at a younger age, present with more advanced liver disease, and have shorter survival times than the general population. The mechanisms by which HIV/HBV co-infection accelerates liver disease remain poorly defined. Enhanced liver pathology may result from persistent immune activation, chronic inflammation, and exposure to viral proteins not eliminated by current therapies. Macrophages infected with HIV secrete a variety of viral proteins, and hepatocytes infected with HBV secrete high quantities of the envelope protein HBsAg into the bloodstream, even in the absence of active replication. To investigate this, we developed a multiparametric assay pipeline to study HIV infection in multiple types of human myeloid cells. Using this pipeline, we modeled co-infection by exposing HIV-infected macrophages to HBV-derived proteins. Treatment with HBsAg led to serotype-dependent effects on HIV replication, viral protein production, and macrophage cytokine responses, including alterations in IL-1[beta] and TNF-[alpha] levels. These data suggest that circulating HBV proteins influence HIV replication and immune activation within myeloid cells. These results provide novel insight into how HBV may exacerbate HIV-associated liver disease and underscore the importance of understanding macrophage responses in the context of viral co-infection.
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Details
- Title
- Establishing a model of HIV infection in macrophages to assess HIV / HBV co-infection driven liver disease
- Creators
- Alexis C. Brantly
- Contributors
- Michael R. Nonnemacher (Advisor)Peter J. Gaskill (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xvi, 246 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991022080355604721