title: Epithelial Barriers in Murine Skin during Herpes Simplex Virus 1 Infection: The Role of Tight Junction Formation.
abstract: Herpes simplex virus 1 has to overcome skin or mucosa barriers to infect its human host. The impact of the various barrier functions on successful viral invasion is not known. On ex vivo infection of murine skin, we observed efficient invasion only via the basal epidermal layer when the dermis was removed. Here, we investigated how wounding and intercellular junction formation control successful viral entry. After wounding of skin samples or removal of the stratum corneum, infected cells were rarely detected. On the basis of infection studies in epidermis from IFN-stimulated mice, we assume that mechanical wounding does not lead to an antiviral state that impedes infection. When we infected human skin equivalents, we observed entry only into unstratified keratinocytes or after wounding of fully stratified cultures. Reduced infection of keratinocytes after calcium-induced stratification confirmed the impact of junction formation. To assess the effect of functional tight junctions, stratified cultures of polarity regulator partitioning-defective-3- or E-cadherin-deficient keratinocytes were infected. As the number of infected cells strongly increased with enhanced paracellular permeability, we conclude that the formation of functional tight junctions interferes with viral entry indicating that next to the stratum corneum tight junctions are a major physical barrier for herpes simplex virus 1 invasion into tissue.
authors.affiliation: Center for Biochemistry, University of Cologne, Cologne, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Rahn
authors.affiliation: Center for Biochemistry, University of Cologne, Cologne, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Thier
authors.affiliation: Center for Biochemistry, University of Cologne, Cologne, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Petermann
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-associated Diseases, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rübsam
authors.affiliation: Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Response in Aging-associated Diseases, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Iden
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Response in Aging-associated Diseases, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
authors.forename: Carien M
authors.initials: CM
authors.lastname: Niessen
authors.affiliation: Center for Biochemistry, University of Cologne, Cologne, Germany; Department of Dermatology, University of Cologne, Cologne, Germany. Electronic address: dagmar.moersdorf@uni-koeln.de.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Knebel-Mörsdorf
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism*; D006561:Herpes Simplex / Q000473:pathology*; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012380:Role; D012680:Sensitivity and Specificity; D019108:Tight Junctions / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism* / Q000821:virology