Study tracing the path of Ebola to the skin surface

Ebola is a deadly bleeding disease caused by a virus that is endemic in parts of East and West Africa. Most people know that the main route of human-to-human transmission is through contact with the body fluids of an infected person. However, in more recent outbreaks, such as the 2013-2016 Ebola outbreak in West Africa, infectious Ebola virus (EBOV) has been detected on the skin of people who died from the infection and even later during the infection. This has been proven.

Although there is evidence to suggest that EBOV can be transmitted through human skin contact during the later stages of the disease, little is known about how the virus leaves the body and reaches the skin surface. No.

Researchers at the University of Iowa Health Care and researchers at the Texas Biomedical Research Institute and Boston University traced the cellular pathways the virus uses to cross the inner and outer layers of the skin and emerge on the skin’s surface.

This study identifies a new cell type in the skin that is targeted by EBOV during infection and shows that human skin specimens actively support EBOV infection.

Overall, the findings, published Jan. 1 in Science Advances, suggest that skin surfaces may be one route for person-to-person transmission.

“Despite the skin being the largest organ in the human body, it is woefully understudied compared to most other organs. The interaction of EBOV with skin cells has not been extensively investigated to date. ,” said Dr. Wendy Morley, a professor of microbiology and immunology at the UI. , senior author of the study.

“Our study provides evidence of one mechanistic pathway that EBOV uses to exit the human body. A comprehensive understanding of which cells are targeted during viral infection will help improve antiviral important for the rational development of the approach.”

Human skin model helps track escape of EBOV

A research team led by Morley and Kelly Messingham, Ph.D., UI research professor of dermatology, has developed a new approach to determine which cells in the skin are infected by the Ebola virus. They created a full-thickness human skin explant system. Skin biopsies taken from healthy individuals included both the deep (dermal) and superficial (epidermal) layers of the skin.

To study how the Ebola virus moves through the skin, explants were placed dermal side down in culture medium, added to the culture medium so that the virus particles entered the skin from the bottom, and blood We modeled the outflow of the virus from the skin to the skin surface. The researchers used virus-tracing and cell-tagging techniques to track the virus’ journey through the skin layers to the top surface of the skin and identify which cells were infected over time.

Previous clinical and animal studies have reported that cells within the skin are infected by EBOV, but the specific cells targeted by the virus have not been identified.

In the new study, the researchers showed that EBOV infected several different cell types, including macrophages, endothelial cells, fibroblasts, and keratinocytes in skin explants. Although some of these cell types are also known to be infected with EBOV in other organs, keratinocytes unique to the skin were not previously recognized to support EBOV infection.

Interestingly, virus replication per gram was more intense in the epidermal layer than in the dermal layer. Furthermore, infectious virus was detected on the epidermal surface within 3 days, indicating that the virus spreads rapidly and migrates through the explant to the skin surface.

The researchers also found that human skin explants serve as a complex three-dimensional organ model to study the efficacy of antiviral drugs against EBOV, creating a highly useful and inexpensive new model system for therapeutic testing. We have shown that we can provide this.

Finally, the research team also focused on the interaction of EBOV with two specific skin cell types, fibroblasts and keratinocytes, and identified specific receptors on these cells that allow Ebola virus uptake. has been identified.

“This study investigates 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 for infection,” Messingham said. “Taken together, these findings elucidate the mechanism by which EBOV moves to the skin surface and may explain human-to-human transmission via skin contact.”