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Dissertation
Multi-faceted developmental studies of non-thermal plasma as a therapy for oral infection by herpes simplex virus type 1
Doctor of Philosophy (Ph.D.), Drexel University
Apr 2025
DOI:
https://doi.org/10.17918/00010915
Abstract
Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen that causes infection in ~70% of the world’s population under the age of 50. Most HSV-1 infections are spread through oral contact, causing orofacial cold sores (herpes labialis) as a clinical manifestation of acute infection when the virus is replicating in mucosal epithelial cells. At the same time, HSV-1 infects innervating sensory neurons and travels into the trigeminal ganglia (TG), where it establishes latent infection and a virus reservoir for recurrent reactivation of acute infection. This lifelong persistence is further facilitated by limitations of the host immune response to HSV-1 infection and the drug treatments that are ineffective in eliminating HSV-1 from patients. To address the need for more effective therapies used to treat herpes labialis, we have been investigating the antiviral therapeutic potential of non-thermal plasma (NTP), partially ionized gas containing multiple effectors. Although the impact of NTP on cell-free virus infectivity has been demonstrated, the effects of NTP on infected cells has not been investigated. In our in vitro investigations, direct application of NTP to HSV-1-infected human keratinocytes significantly reduced virus infection. When NTP was applied to cells before HSV-1 infection, reductions in cell susceptibility and virus release were observed. This reduction in keratinocyte susceptibility was consistent with observed NTP-associated changes in N-glycan residues on cell surface molecules potentially involved in HSV-1 attachment. The antiviral activity of NTP on HSV-1-infected cells was subsequently investigated using a lip scarification model of herpes labialis. In these preliminary experiments, NTP treatment of a lesion caused by acute HSV-1 infection resulted in reductions of HSV-1 DNA copy numbers in the lip tissue and in the TG. These preliminary in vivo findings complement our in vitro results and suggest a direct antiviral effect of NTP treatment on acute HSV-1 infection as well as an indirect effect on the establishment of the latent viral reservoir in the TG. In summary, these studies support the development of an NTP-based therapy for herpes labialis and serve as the foundation for further explorations of the antiviral activities of NTP in the context of HSV-1 infection and pathogenesis.
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Details
- Title
- Multi-faceted developmental studies of non-thermal plasma as a therapy for oral infection by herpes simplex virus type 1
- Creators
- Julia Sutter
- Contributors
- Fred C. Krebs (Advisor)Vandana Miller (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xxiii, 337 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991022048718204721