Multi-faceted developmental studies of non-thermal plasma as a therapy for oral infection by herpes simplex virus type 1
Year: 2025
Type: dissertation
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.
DOI: 10.17918/00010915
Authors: Julia Sutter, Fred C. Krebs, Vandana Miller
Language: English
Subfield: Atomic and Molecular Physics, and Optics
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4410003055