Skin may play a hidden role in Ebola infection

Ebola, a severe hemorrhagic disease caused by a virus endemic in parts of East-Central and West Africa, is generally known to spread through contact with bodily fluids from individuals who have the infection. 

Ebola virus on the skin surface

More recent outbreaks, such as the 2013-2016 Ebola epidemic in West Africa, have shown that infectious Ebola virus (EBOV) is also found on the surface of the skin of those who have succumbed to infection or at late times during infection. 

Although this suggests that the virus can be transmitted from skin contact with someone in the later stages of the disease, researchers have not yet fully understood how the virus exits the body and appears on the skin’s surface.

In a recent study, scientists at University of Iowa Health Care, working with colleagues at Texas Biomedical Research Institute and Boston University, have uncovered a cellular route that EBOV uses to traverse the inner and outer layers of skin and emerge onto the surface. 

The researchers identified new cell types within the skin that are targeted by EBOV during infection and confirms that human skin tissues actively sustain EBOV infection. 

Possible route of Ebola infection

The results, published in the journal Science Advances, suggest that the skin’s surface may be one possible route 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,” said study senior author Wendy Maury, a professor of microbiology and immunology at the University of Iowa. 

“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.”

Human skin model for tracking Ebola

The research team, guided by Maury and Kelly Messingham, a research professor of dermatology at the University of Iowa, designed a new method for discovering which skin cells are infected by Ebola virus. 

They constructed a human skin explant system using full-thickness biopsies from healthy individuals, preserving both the deeper (dermal) and surface (epidermal) layers of skin.

Next, the team placed these explants dermal side down in culture media, adding virus particles to simulate how EBOV would move from the bloodstream outward toward the skin’s exterior. 

This setup let the researchers use specialized tracing and labeling techniques to observe how the virus progressed from one layer of skin to the next, tracking which cells became infected as time passed.

Skin cells prone to Ebola infection

Prior clinical and animal studies indicated that skin cells could become infected with EBOV, yet they did not identify the particular cells involved. 

In this work, the authors showed that EBOV infects several cell types in the skin explant, including macrophages, endothelial cells, fibroblasts, and keratinocytes. 

Some of these cells are also infected by EBOV in other tissues, but keratinocytes – particular to skin – had not been previously recognized as an EBOV replication site.

Notably, the virus appeared to replicate more actively in the epidermal layer than in the dermal layer when compared on a per-gram basis. Within three days, infectious virus was detected at the epidermal surface, underscoring the virus’s ability to rapidly move through skin to the surface.

Tool for exploring new therapies

In addition to mapping how the virus travels through the skin, the scientists demonstrated that human skin explants offer a realistic, three-dimensional model for examining potential antiviral treatments against EBOV. This model could be an economical and valuable tool for exploring new therapies.

“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,” Messingham said. 

“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.”

New insights into Ebola infection 

Beyond its discoveries about the skin, the research also zoomed in on interactions between the Ebola virus and two particular skin cell types, fibroblasts and keratinocytes. 

The team found specific receptors on these cells that facilitate the virus’s entry, adding further clarity on how EBOV infects skin on a molecular level.

By clarifying one route the virus may take to exit the body, these findings expand our knowledge of Ebola’s spread and highlight why skin-to-skin contact in advanced cases of infection can pose such a risk. 

Ongoing public health concern

Understanding these pathways, and identifying the cell types that the virus relies on, can influence future efforts to develop effective treatments and prevention measures.

This work also sets the stage for further investigations into how EBOV might exploit other organs or tissues and suggests potential ways to block the virus’s path at the skin level. 

With Ebola remaining an ongoing global health concern, insights like these can help scientists target the virus more effectively and better protect those at risk of infection.

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