Model of Human Skin Shows How Ebola Virus Reaches the Skin’s Surface
The findings spotlight a highly potent source of Ebola virus shedding with the potential for person-to-person transmission
A new study published in the journal Science Advances answers a long-held question: How does Ebola virus target skin cells to reach the skin’s surface during the final stages of infection?
The research, involving human skin explant models and no viral engineering, shows how this deadly virus infects at least three cell types in the lower dermis and then permeates the outermost epidermis via infiltration of another cell type.
Overall, the findings spotlight a highly potent source of Ebola virus shedding with the potential for person-to-person transmission.
During the severe 2013–2016 West African Ebola outbreak, scientists observed that Ebola virions, antigens, and RNA shed from the epidermis in the last phase of infection. Past studies in animal models have corroborated these observations.
However, the way that Ebola virus heads to the skin’s surface has remained a mystery.
Now, Kelly Messingham, PhD, and colleagues describe this phenomenon. They examined ex vivo human tissue viral cultures over the course of 17 days, noting how the virus traveled by infecting select cell groups from the undermost dermis to the outermost, or apical, epidermis.
Endothelial, myeloid, and fibroblast cells in the dermis were primarily positive for Ebola antigen. Within three days, the virus reached the apical epidermis and populated cells there called keratinocytes.
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Messingham and colleagues performed additional tests using purified human keratinocytes and fibroblasts to see which intracellular mechanisms supported Ebola infiltration. They saw that the endosomal protein, NPC1, and phosphatidylserine receptor, AXL, were critical.
“Our findings define a route through which infectious virus traverses the skin to the epidermal surface, thereby potentially contributing to person-to-person transmission,” the authors write. Referencing their human skin explant model, they add: “Furthermore, we highlight the utility of this readily available model system for antiviral studies, providing a highly relevant platform for testing drugs.”