New Model for Studying Ebola Virus Pathogenesis

Ebola is a fatal hemorrhagic disease caused by a virus that is found in parts of East-Central and West Africa. Most individuals are aware that the major mode of person-to-person transmission is through contact with an infected person’s bodily fluids. However, more recent outbreaks, such as the 2013-2016 Ebola pandemic in West Africa, have shown that infectious Ebola virus (EBOV) can be discovered on the skin’s surface of persons who have died from infection or at late stages of infection.

Although evidence suggests that EBOV can be transmitted by skin contact with a person in the late stages of the disease, nothing is known about how the virus exits the body and reaches the skin’s surface.

In a new study, researchers at the University of Iowa Health Care, along with colleagues at the Texas Biomedical Research Institute and Boston University, traced the virus’s cellular route through the inner and outer layers of skin before emerging onto the skin’s surface.

The study finds additional cell types in the skin that EBOV targets during infection and demonstrates that human skin specimens actively promote EBOV infection. Overall, the findings, published in Science Advances on January 1^st, 2025, show that the skin's surface could be a pathway of person-to-person transmission.

The skin is the largest organ in the human body yet is woefully understudied compared to most other organs. Interactions of EBOV with skin cells have not previously been extensively examined. Our work provides evidence for one mechanistic avenue that EBOV uses to exit from the human body. A comprehensive understanding of which cells are targeted during virus infection is critical for rational development of antiviral approaches.”

Wendy Maury, PhD, Study Senior Author and Professor, University of Iowa

Human Skin Model Helps Trace EBOV Escape

The study team, coordinated by Maury and Kelly Messingham, PhD, UI research professors of dermatology, devised a new method to determine whether cells in the skin are infected with the Ebola virus. They developed a human skin explant system utilizing full-thickness skin biopsies from healthy people, which included both the deeper (dermal) and surface (epidermal) layers of skin.

Explants were placed dermal side down in culture media, and virus particles were added to the media so that they entered the skin from the underside, simulating virus egress from the blood to the skin's surface.

This allowed researchers to examine how the Ebola virus spreads through the skin. By tracking the virus's progression from the skin's layers to the upper surface of the skin, the researchers were able to determine which cells were infected over time using virus-tracing and cell-tagging approaches.

Although EBOV has been shown to infect skin cells in previous clinical and animal research, the precise cells that the virus targets have not yet been determined.

The researchers demonstrated in the new study that EBOV infected a variety of cell types in the skin explant, including fibroblasts, keratinocytes, endothelial cells, and macrophages.

While several of these cell types have been reported to be infected with EBOV in other organs, keratinocytes, which are specific to the skin, were not previously recognized as supporting EBOV infection.

Remarkably, on a per-gram basis, virus replication was stronger in the epidermal layer than in the dermal layers. Furthermore, within three days, the infectious virus was found on the epidermal surface, suggesting that it travels quickly and penetrates the explants to reach the skin’s surface.

Additionally, the researchers demonstrated that human skin explants can be used as intricate, three-dimensional organ models to examine how well antivirals work against EBOV, offering a novel, practical, and affordable model system for therapeutic testing.

Last but not least, the group also examined how EBOV interacted with two distinct skin cell types—fibroblasts and keratinocytes—and discovered particular receptors on these cells that allow Ebola virus uptake.

This study explores the role of the skin as a potential route of Ebola virus infection and identifies, for the first time, several cell types in the skin that are permissive to infection. In total, these findings elucidate a mechanism by which EBOV traffics to the skin’s surface and may explain person-to-person transmission via skin contact.”

Kelly Messingham, Research Professor, University of Iowa