During primary infection, herpes simplex virus 1 (HSV-1) enters human skin or mucosa and establishes lifelong latency in sensory neurons. The skin is normally well protected from invading pathogens as the epithelium forms effective barriers. How HSV-1 can overcome this barrier in vivo remains to be shown. One prominent example for successful HSV-1 skin invasion is eczema herpeticum, a disseminated HSV-1 infection and severe complication of atopic dermatitis (AD). In lesional skin of AD patients, the mechanical skin barrier consisting of the stratum corneum and tight junctions in the stratum granulosum is impaired. Whether the higher susceptibility to HSV-1 infection in AD patients is due to epidermal barrier defects and/or chronic inflammation is still speculative. To understand the role of epidermal barrier defects in HSV-1 skin invasion, we performed ex vivo infection assays with skin taken from AD patients. These revealed that HSV-1 invaded lesional skin from the apical surface, which was in contrast to healthy skin, where only skin edges with tissue integrity loss allowed access to basal cells. Immunostainings showed a redistribution of various barrier components and supported facilitated HSV-1 infection due to impaired epidermal barriers in the lesional AD skin. To demonstrate a direct correlation between individual barrier defects and enhanced viral invasion, human 3D epidermal models were adopted. HSV-1 infection studies confirmed the important roles of the stratum corneum and the integrity of tight junctions in hindering HSV-1 entry in keratinocytes. Moreover, the 3D cultures provide a tool to introduce phenotypic inflammation-induced hallmarks of AD.

ESDR122 - Ex vivo infection of skin from atopic dermatitis patients reveals facilitated invasion of herpes simplex virus 1

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING