Dissertation
Development of a high throughput high content imaging viral titer assay to investigate the effect of substance misuse on HIV-1 replicative dynamics in hMDMs
Doctor of Philosophy (Ph.D.), Drexel University
Oct 2023
DOI:
https://doi.org/10.17918/00001933
Abstract
Over 38 million people are infected with HIV-1 worldwide and in the past four decades of the HIV-1 pandemic there have been numerous failures and successes. Most notably, the successful development of antiretroviral therapies has contributed greatly to the increased longevity of people living with HIV-1 (PLWH). However, with antiretroviral control, the counterbalance is that HIV-1 is a chronic infection, latently infecting reservoirs, and inflammation over long periods of time that lead to HIV-associated comorbidities affecting entire body systems such as the central nervous system, cardiovascular, respiratory, and gastrointestinal systems. Modeling how HIV-1 interacts in the cellular niches of these reservoirs is an essential part of unraveling the underlying mechanisms associated with the development of disease and exacerbation of clinical HIV-1 presentation. We discuss the historical perspectives of HIV-1, summarizing the four-decade long pandemic, HIV-1 biology, and the epidemiological burden of substance misuse as a rationale for investigating HIV-1 viral dynamics. To aid in our investigations of viral dynamics, we have developed a novel high throughput and rapid high content imaging viral titer assay that aims to assess viral maturation and in combination with other infection kinetic studies can reveal the efficiency of viral replication and how that may change in different co-morbid conditions such as substance misuse. Our data demonstrate that we can reliably assess viral titer, and by extension viral maturation in viral stocks, and experimental in vitro models of the substance misuse downstream effect of dopamine exposure, which supports previous published work. We also demonstrate preliminary findings that suggest cocaine has the capability to also exacerbate HIV-1 infection in the absence of dopamine in primary hMDMs. These studies and future work will allow for more precise interrogation of HIV-1 viral dynamics that underscore undefined mechanisms of viral replication, spread, and disease progression in cellular and tissue reservoirs.
Metrics
89 File views/ downloads
33 Record Views
Details
- Title
- Development of a high throughput high content imaging viral titer assay to investigate the effect of substance misuse on HIV-1 replicative dynamics in hMDMs
- Creators
- Teresa Marie LuPone
- Contributors
- Peter J. Gaskill (Advisor)Alison Carey (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xii, 245 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991021819115504721