Ebola is a fatal hemorrhagic disease caused by a virus found in east-central and western Africa. It is known that the virus is spread primarily through contact with the bodily fluids of infected people, but recent outbreaks, including one in West Africa from 2013 to 2016, have revealed another potential route of transmission.
Researchers have discovered that the contagious Ebola virus (EBOV) is present on the surface of the skin, especially in patients late in the disease or after death. Despite this discovery, the process by which the virus spreads from the body to the surface of the skin remains poorly understood.
A new study by researchers at the University of Iowa College of Health Care, in collaboration with Texas Biomedical Research Institute and Boston University, traces the cellular pathway that EBOV takes through the skin layers to reach the skin surface. This study identifies the specific skin cell types targeted by the virus and demonstrates that human skin actively supports EBOV infection. The findings, published today (January 1) in Science Advances, indicate that the skin surface may be an important route for human-to-human transmission of the virus.
"The skin is the largest organ in the human body, yet it has been poorly studied compared to most other organs. The interaction of EBOV with skin cells has never been extensively studied before," said Dr. Wendy Maury, senior author of the study and a professor of microbiology and immunology at the University of California, Los Angeles. "Our work provides evidence for a mechanism by which EBOV is shed from the body. A comprehensive understanding of which cells are targeted during viral infection is critical for the rational development of antiviral approaches."
A research team led by Maury and Kelly Messingham, Ph.D., UI research professor of dermatology, developed a new method to examine which cells within the skin are infected by Ebola virus. They used full-thickness skin biopsies from healthy individuals to create a human skin explant system that includes both deep (dermal) and superficial (epidermal) layers of skin.
To study how Ebola virus moves in the skin, the researchers placed the explants dermis-side down in culture medium and added virus particles to the culture medium so that they entered the skin from the bottom, simulating the process of the virus escaping from the blood to the skin surface. The researchers used virus tracking and cell labeling techniques to track the virus as it travels through the skin layers to the upper surface of the skin to determine which cells are infected over time.
Previous clinical and animal studies have reported that cells within the skin can be infected with Ebola virus, but the specific cells targeted by the virus have not been identified. In the new study, the team found that EBOV infected several different cell types in skin explants, including macrophages, endothelial cells, fibroblasts and keratinocytes. Although some of these cell types are also infected by EBOV in other organs, keratinocytes unique to the skin have never been found to support EBOV infection before.
Interestingly, on a per gram basis, viral replication was stronger in the epidermis than in the dermis. Furthermore, infectious virus was detectable on the epidermal surface within three days, indicating rapid spread of the virus through explants and movement to the skin surface.
The researchers also showed that human skin explants can serve as complex three-dimensional organ models for studying the efficacy of antiviral drugs against EBOV, providing a new, highly useful and inexpensive model system for treatment testing.
Finally, the team also focused on the interaction of Ebola virus with two specific skin cell types, fibroblasts and keratinocytes, and identified specific receptors on these cells that allow uptake of Ebola virus.
"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 allow infection," Messingham said. "Together, these findings shed light on the mechanism by which Ebola virus spreads to skin surfaces and may explain human-to-human transmission through skin-to-skin contact."
Compiled from /scitechdaily