Herpes simplex virus type 1 infection of mucosa and skin: identification of invasion routes

• Applicant: Professorin Dr. Dagmar Knebel-Mörsdorf
• Subject Area: Virology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 231769905

The research objective of this proposal is to determine how herpes simplex virus type 1 (HSV-1) enters stratified epithelia using an ex vivo infection assay. Since the human oral cavity represents the primary entry portal of HSV-1, we initiated infection studies in human oral mucosa to identify the entry site. To gain access to a highly polarized and protective tissue such as mucosa or skin HSV-1 has to overcome the barrier functions of the epithelium comprising immune defences as well as physical barriers. Our initial studies suggest that the virus cannot enter intact mucosa samples unless the epidermis is separated from the dermis followed by infection of the basal keratinocytes. Therefore, our working hypothesis is that the mucosa has to be mechanically injured or pathologically altered to allow infection. This is in line with the general assumption that infection of human skin needs at least microlesions. In addition to human mucosa we will infect murine skin ex vivo to establish wounding strategies that allow HSV-1 entry. Furthermore, we will address whether epidermal barrier defects established in mouse models result in enhanced HSV-1 entry from skin surfaces. To date the cellular and molecular mechanisms underlying the initial entry of HSV-1 into skin or mucosa of its human host are not understood. Determining the entry route and identifying the factors that allow HSV-1 to reach its receptors and to enter keratinocytes is a major challenge and this research aims to establish experimental tools that help to characterize HSV-1 entry into tissue.

• DFG Programme: Research Grants