Dissertation
Ebola virus skin infections: defining viral entry, trafficking, and tropism
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2025
DOI: 10.25820/etd.008204
Abstract
Ebola virus (EBOV) is a highly pathogenic filovirus that causes severe hemorrhagic fever in humans. While transmission is typically attributed to direct contact with bodily fluids, the contribution of peripheral tissues such as the skin to EBOV pathogenesis and transmission remains poorly defined. During the 2014–2016 West Africa outbreak, anecdotal reports linked numerous cases to participation in traditional funeral rites, suggesting the possibility that EBOV may persist on or within the skin even after death.
This dissertation investigates the role of skin as a site of EBOV infection, replication, and potential viral shedding. Using ex vivo human skin explants, I demonstrate that EBOV traffics through the explant from the dermis to the epidermis, productively infecting dermal immune cells, stromal cells, and basal keratinocytes. Viral RNA and infectious virus were also detected at the apical surface of the epidermis, suggesting that skin may serve as an unrecognized source of person-to-person transmission. These findings were supported in non-human primates and mouse models of infection. Additionally, infection of the mouse model revealed patterns of focal viral localization within dermal layers —supporting nonuniform spread —and around appendageal structures, including hair follicles and sebaceous glands.
Despite the presence of EBOV RNA and antigen in skin that is distal to the site of infection, inflammatory gene expression in these tissues remained unexpectedly low. This contrasted sharply with the strong inflammatory responses observed in visceral tissues from the same animals, suggesting that EBOV may actively dampen or evade immune responses in the skin, allowing replication to proceed with minimal inflammation, particularly at distal sites.
Notably, using a BSL2-compatible model virus (rVSV/EBOV GP), infectious virus was detectable at the surface of mouse skin distal to the site of injection, even in the absence of rash. Critically, this suggest that viral shedding may occur prior to or without visible skin involvement. Further, mechanistic studies revealed that the phosphatidylserine receptor AXL is required for efficient skin infection when virus is applied topically and is required for optimal keratinocyte and skin fibroblast infection. However, systemic viral dissemination was not dependent upon AXL expression as titers were unchanged in AXL–/– mice. This suggests that topical EBOV infection can drive systemic dissemination independently of keratinocyte-dependent infection. These findings support a model in which EBOV spreads through the skin not diffusely, but in highly focal patterns that may evade detection yet permit viral egress.
In addition to defining skin as a site of viral replication and shedding, I also show that skin exposure can elicit protective immune responses. Mice exposed to EBOV via the skin developed robust GP-specific antibody responses even in the absence of productive systemic infection, suggesting that the skin may serve as a viable route for vaccine delivery.
Together, these findings establish the skin as a dynamic and underappreciated interface for EBOV transmission, replication, and immune activation. This work redefines the cutaneous landscape of EBOV pathogenesis and highlights novel pathways of surface shedding and viral entry with direct implications for transmission risk and countermeasure development.
Details
- Title: Subtitle
- Ebola virus skin infections: defining viral entry, trafficking, and tropism
- Creators
- Paige Taylor Richards
- Contributors
- Wendy Maury (Advisor)Kelly Messingham (Committee Member)Richard Roller (Committee Member)Aloysius Klingelhutz (Committee Member)Stanley Perlman (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Microbiology
- Date degree season
- Autumn 2025
- DOI
- 10.25820/etd.008204
- Publisher
- University of Iowa
- Number of pages
- xxii, 262 pages
- Copyright
- Copyright 2025 Paige Taylor Richards
- Language
- English
- Date submitted
- 08/28/2025
- Description illustrations
- illustrations, graphs, tables
- Description bibliographic
- Includes bibliographical references (pages 223-262).
- Public Abstract (ETD)
- Ebola virus causes a severe and often deadly disease in humans, with fatality rates ranging from 25 90%. To better prevent future outbreaks, it is important to understand how the virus spreads from person-to-person. During the largest outbreak from 2014 to 2016, many people became infected after attending funerals or touching the bodies of those who had died from Ebola. This raised concerns that the virus might be present on the skin and able to spread through contact. My research explores how Ebola interacts with the skin. I used a model of human skin to study infection in a way that closely reflects what happens in people, and I compared those results to animal models to understand how the infection behaves in the body. I found that Ebola can infect the full thickness of human skin including cells in the surface layers and may even exit through the skin. In animals, I saw similar patterns with additional staining around hair follicles, even when there was no visible rash. These findings give us a clearer picture of how Ebola might spread through skin contact. I also discovered that applying Ebola virus to the skin of animals resistant to systemic infection still triggered protective immune responses. This suggests the skin could be a useful site for delivering vaccines. Altogether, my work deepens our understanding of how Ebola spreads through the skin and points to new avenues for prevention and treatment.
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9985135249002771
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