Ebola is a deadly hemorrhagic disease caused by a virus endemic in parts of East and West Africa. Most people know that the main route of person-to-person transmission is through contact with the bodily fluids of an infected person. But more recent outbreaks, including the 2013 to 2016 Ebola outbreak in West Africa, have demonstrated that the infectious Ebola virus (EBOV) is also present on the skin surface of those who have succumbed to the disease. infection or at late times of infection. Although evidence suggests that EBOV can be transmitted through skin contact with a person in later stages of the disease, very little is known about how the virus exits the body and reaches the surface of the skin.
In a new study, researchers from the University of Iowa Health Care and colleagues from the Texas Biomedical Research Institute and Boston University traced the cellular route used by the virus to pass through the inner and outer layers of the skin and emerge on the surface of the skin. The study identifies new types of skin cells targeted by EBOV during infection and shows that human skin samples actively support EBOV infection. Overall, the results, published on January 1 in Scientific advancessuggest that the skin surface could be a route of person-to-person transmission.
“The skin is the largest organ in the human body, but it is unfortunately understudied compared to most other organs. The interactions of EBOV with skin cells have not yet been studied extensively,” says Wendy Maury, PhD, professor of microbiology and immunology at the UI. author of the study.
Our work provides evidence for a mechanistic pathway used by EBOV to exit the human body. A comprehensive understanding of the cells targeted during viral infection is essential for the rational development of antiviral approaches.
Wendy Maury, PhD, professor of microbiology and immunology, University of Iowa Health Care
Human skin model helps trace EBOV leak
The research team, led by Maury and Kelly Messingham, PhD, research professor of dermatology at the UI, developed a new approach to examine which skin cells are infected by the Ebola virus. They created a human skin explant system using full-thickness skin biopsies from healthy individuals, which contained both deeper (cutaneous) and superficial (epidermal) layers of skin.
To study how the Ebola virus moves through the skin, explants were placed dermal side down in culture media and virus particles were added to the media so that they penetrated the skin from below, modeling thus the exit of the virus from the blood to the surface of the skin. Researchers used virus tracing and cell labeling techniques to follow the virus’s journey through the skin layers to the upper surface of the skin, identifying infected cells over time.
Previous clinical and animal studies had reported that skin cells were infected by EBOV, but the specific cells targeted by the virus had not been identified.
-In the new study, the team showed that EBOV infected several different cell types in the skin explant, including macrophages, endothelial cells, fibroblasts and keratinocytes. Although some of these cell types are also infected by EBOV in other organs, keratinocytes, which are unique to the skin, have not previously been appreciated for supporting EBOV infection. .
Interestingly, virus replication was more robust in the epidermal layer than in the dermal layers, per gram. Additionally, infectious virus was detected on the surface of the epidermis within three days, indicating that the virus spreads rapidly and travels through the explants to the skin surface.
The researchers also showed that human skin explants can serve as complex three-dimensional organ models to study the effectiveness of antiviral drugs against EBOV, providing a highly useful and inexpensive new model system for therapeutic testing.
Finally, the team also focused on the interactions of EBOV with two specific types of skin cells, fibroblasts and keratinocytes, and identified specific receptors on these cells that allow the capture of the Ebola virus.
“This study explores the role of the skin as a potential route of Ebola infection and identifies, for the first time, several types of skin cells permissive to infection,” says Messingham. “Altogether, these results elucidate a mechanism by which EBOV travels to the skin surface and may explain person-to-person transmission through skin contact. »
In addition to Messingham and Maury, the study team included researcher Paige Richards, Anthony Fleck, Radhika Patel, Jonah Elliff, Samuel Connell, Tyler Crowe, Juan Munoz Gonzalez, Françoise Gourronc, Jacob Dillard and Aloysius Klingelhutz. Marija Djurkovic and Olena Shtanko of the Texas Biomedical Research Institute, as well as Robert Davey of Boston University were also part of the team.
The research was funded in part by grants from the National Institute of Allergy and Infectious Diseases.
