Universität zu Köln

Thier, Katharina, Petermann, Philipp, Rahn, Elena, Rothamel, Daniel, Bloch, Wilhelm and Knebel-Moersdorf, Dagmar (2017). Mechanical Barriers Restrict Invasion of Herpes Simplex Virus 1 into Human Oral Mucosa. J. Virol., 91 (22). WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5514

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Abstract

Oral mucosa is one of the main target tissues of the human pathogen herpes simplex virus 1 (HSV-1). How the virus overcomes the protective epithelial barriers and penetrates the tissue to reach its receptors and initiate infection is still unclear. Here, we established an ex vivo infection assay with human oral mucosa that allows viral entry studies in a natural target tissue. The focus was on the susceptibility of keratinocytes in the epithelium and the characterization of cellular receptors that mediate viral entry. Upon ex vivo infection of gingiva or vestibular mucosa, we observed that intact human mucosa samples were protected from viral invasion. In contrast, the basal layer of the oral epithelium was efficiently invaded once the connective tissue and the basement membrane were removed. Later during infection, HSV-1 spread from basal keratinocytes to upper layers, demonstrating the susceptibility of the stratified squamous epithelium to HSV-1. The analysis of potential receptors revealed nectin-1 on most mucosal keratinocytes, whereas herpesvirus entry mediator (HVEM) was found only on a subpopulation of cells, suggesting that nectin-1 acts as primary receptor for HSV-1 in human oral mucosa. To mimic the supposed entry route of HSV-1 via microlesions in vivo, we mechanically wounded the mucosa prior to infection. While we observed a limited number of infected keratinocytes in some wounded mucosa samples, other samples showed no infected cells. Thus, we conclude that mechanical wounding of mucosa is insufficient for the virus to efficiently overcome epithelial barriers and to make entry-mediating receptors accessible. IMPORTANCE To invade the target tissue of its human host during primary infection, herpes simplex virus (HSV) must overcome the epithelial barriers of mucosa, skin, or cornea. For most viruses, the mechanisms underlying the invasion into the target tissues of their host organism are still open. Here, we established an ex vivo infection model of human oral mucosa to explore how HSV can enter its target tissue. Our results demonstrate that intact mucosa samples and even compromised tissue allow only very limited access of HSV to keratinocytes. Detailed understanding of barrier functions is an essential precondition to unravel how HSV bypasses the barriers and approaches its receptors in tissue and why it is beneficial for the virus to use a cell-cell adhesion molecule, such as nectin-1, as a receptor.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thier, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Petermann, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Rahn, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED Rothamel, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Knebel-Moersdorf, Dagmar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-212922
DOI:	10.1128/JVI.01295-17
Journal or Publication Title:	J. Virol.
Volume:	91
Number:	22
Date:	2017
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5514
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LANGERHANS CELLS; ENTRY MEDIATOR; MURINE EPIDERMIS; TYPE-1; SKIN; EXPRESSION; PROLIFERATION; HERPESVIRUSES; INFECTION; ANTIGEN Multiple languages Virology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21292