Ebola virus’ hidden target: virus transmission to and infection of skin

Abstract

Ebola virus (EBOV) remains one of the World Health Organization’s top 10 threats to global health, despite the availability of a U.S. Food and Drug Administration-approved vaccine. EBOV spreads through human-to-human contact, yet the role of skin in viral transmission remains unclear. Here, we identify skin as a site of EBOV infection, serving as a potential portal for entry into and egress from the body. In vivo , infectious virions and viral RNA increased in the skin over time, localizing to dermal myeloid and stromal cells and to cells within and surrounding hair follicles, suggesting a novel mechanism for viral shedding. Skin infection was patchy and associated with minimal inflammation, despite significant viral loads. Using a surrogate EBOV model, we demonstrate that systemic infection can occur following topical administration through abraded skin and requires phosphatidylserine receptor, AXL, for optimal infection of skin. These findings redefine the role of skin in EBOV pathogenesis, with implications for barrier-targeted interventions.