title: Invasion of Herpes Simplex Virus Type 1 into Murine Epidermis: An Ex Vivo Infection Study.
abstract: Herpes simplex virus type 1 (HSV-1) invades its human host via the skin or mucosa. We aim to understand how HSV-1 overcomes the barrier function of the host epithelia, and for this reason, we established an ex vivo infection assay initially with murine skin samples. Here, we report how tissue has to be prepared to be susceptible to HSV-1 infection. Most efficient infection of the epidermis was achieved by removing the dermis. HSV-1 initially invaded the basal epidermal layer, and from there, spreading to the suprabasal layers was observed. Strikingly, in resting stage hair follicles, only the hair germ was infected, whereas the quiescent bulge stem cells (SCs) were resistant to infection. However, during the growth phase, infected cells were also detected in the activated bulge SCs. We demonstrated that cell proliferation was not a precondition for HSV-1 invasion, but SC activation was required as shown by infection of aberrantly activated bulge SCs in integrin-linked kinase (ILK)-deficient hair follicles. These results suggest that the status of the bulge SCs determines whether HSV-1 can reach its receptors, whereas the receptors on basal keratinocytes are accessible irrespective of their proliferation status.
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: Philipp
authors.initials: P
authors.lastname: Petermann
authors.affiliation: Center for Biochemistry, University of Cologne, Cologne, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Thier
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sports University, Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.affiliation: Paul Gerson Unna Group 'Skin Homeostasis and Ageing', Max Planck Institute for Biology of Ageing, Cologne, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Morgner
authors.affiliation: Paul Gerson Unna Group 'Skin Homeostasis and Ageing', Max Planck Institute for Biology of Ageing, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Wickström
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; D004492:Edetic Acid / Q000494:pharmacology; D010450:Endopeptidases / Q000494:pharmacology; D004817:Epidermis / Q000821:virology*; D018859:Hair Follicle / Q000821:virology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D017874:Immediate-Early Proteins / Q000502:physiology; D008544:Melanocytes / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D019108:Tight Junctions / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000502:physiology
chemical_list: D017874:Immediate-Early Proteins; D004492:Edetic Acid; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D010450:Endopeptidases; C023139:dispase