Ex vivo infection of human skin with herpes simplex virus 1 reveals mechanical wounds as insufficient entry portals via the skin surface
Herpes simplex virus 1 (HSV-1) enters its human host via the skin or mucosa. The open question is how the virus invades this highly protective tissue in vivo to approach its receptors in the epidermis and initiate infection. Here, we performed ex vivo infection studies in human skin to investigate how susceptible the epidermis and dermis are to HSV-1 and whether wounding facilitates viral invasion. Upon ex vivo infection of complete skin, only sample edges demonstrated infected cells. After removal of the dermis, HSV-1 efficiently invaded the basal layer, and from there, gained access to suprabasal layers supporting a high susceptibility of the epidermis. In contrast, only single infected cells were detected in the papillary layer of the separated dermis. Interestingly, after wounding, nearly no infection of the epidermis was observed via the skin surface. However, if the wounding of the skin samples led to breaks through the dermis, HSV-1 infected mainly keratinocytes via the wounded dermis. The application of latex beads revealed only occasional entry via the wounded dermis, however, facilitated penetration via the wounded skin surface. Thus, we suggest that the wounded human skin surface allows particle penetration but still provides barriers that prevent HSV-1 invasion.