Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that can target skin to establish infection in the epithelium. Since the human skin provides effective barriers against pathogens under normal conditions, HSV-1 must find opportunistic pathways in order to penetrate the skin and initiate infection. As mechanical wounds of the human skin surface do not provide ad hoc entry portals for HSV-1, we explored the role of pathological skin conditions. Ex vivo infection studies revealed successful invasion in lesional AD skin implying that the virus can overcome both the stratum corneum and the tight junction barriers. To dissect the parameters that contribute to HSV-1 invasion, we treated human skin without pre-existing barrier defects with interleukin (IL)-4 and IL-13 to investigate whether Th2 cytokine-driven inflammation already induces modifications that allow viral penetration. Strikingly, we detected infected cells in the epidermis indicating that the IL-induced, AD-like skin phenotype can indeed facilitate HSV-1 invasion. Potential modifications allowing for facilitated viral access include impaired tight junctions, an altered stratum corneum, or a redistribution of the HSV-1 receptor nectin-1. Studies using human epidermal equivalents highlighted the importance of functional tight junctions in addition to the stratum corneum in restricting HSV-1 entry and provide a tool to mimic the pathological alterations in AD skin that allow HSV-1 invasion.

ESDR199 - Ex vivo infection of human skin with herpes simplex virus 1: Lesional AD skin and IL-4/IL-13-stimulated skin provide facilitated viral invasion

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.