title: Herpes simplex virus type 1 exhibits a tropism for basal entry in polarized epithelial cells.
abstract: Herpes simplex virus type 1 (HSV-1) enters its host via epithelia and spreads to neuronal cells where latency is established. Hence, the in vivo route of infection relies on penetration and subsequent passage of HSV-1 through highly polarized cells. Infection studies were performed in both polarized MDCKII cells and primary human keratinocytes to gain insight into the pathway of virus entry into individual epithelial cells. Early viral gene expression was barely detectable in confluent MDCKII cells, even at high m.o.i. However, after wounding the cell layer, infected cells were observed next to the wound, where basolateral membranes were accessible. In subconfluent monolayers, MDCKII cells are organized in islets. After infection, viral capsids and early viral gene expression were detectable in peripheral cells of islets, supporting virus penetration via basolateral membranes. Further infection studies were performed in human keratinocytes, which represent the primary target cells for HSV-1 infection in vivo. In primary keratinocytes grown as monolayer cultures and wounded prior to infection, HSV-1 infection led to early viral gene expression predominantly in cells next to the wound. When stratifying cultures of primary human keratinocytes were infected, early viral gene expression was localized to peripheral cells of basal keratinocytes. Finally, infection of epithelial tissue such as human foreskin epithelia demonstrated HSV-1 entry exclusively via basal cell layers. Staining of the potential coreceptor nectin-1/HveC revealed no correlation of receptor localization and virus entry sites in keratinocytes. These results provide first evidence for a virus entry mechanism that relies on the accessibility to basal surfaces of epithelial tissue and to basolateral membranes, both in MDCKII and primary keratinocytes.
authors.affiliation: Max Planck Institute for Neurological Research, University of Cologne, Gleuelerstrasse 50, D-50931 Cologne, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Schelhaas
authors.affiliation: Max Planck Institute for Neurological Research, University of Cologne, Gleuelerstrasse 50, D-50931 Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Jansen
authors.affiliation: Department of Dermatology, University of Cologne, Gleuelerstrasse 50, D-50931 Cologne, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Haase
authors.affiliation: Department of Neurology, University of Cologne, Gleuelerstrasse 50, D-50931 Cologne, Germany.|Max Planck Institute for Neurological Research, University of Cologne, Gleuelerstrasse 50, D-50931 Cologne, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Knebel-Mörsdorf
mesh_terms: D000818:Animals; D002213:Capsid / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis; D002478:Cells, Cultured; D046508:Culture Techniques; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism / Q000821:virology*; D000075983:Nectins; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication
chemical_list: D015815:Cell Adhesion Molecules; D017874:Immediate-Early Proteins; C000619010:NECTIN1 protein, human; D000075983:Nectins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1