Universität zu Köln

De la Cruz, Nydia C., Moeckel, Maureen, Wirtz, Lisa, Sunaoglu, Katharina, Malter, Wolfram, Zinser, Max and Knebel-Moersdorf, Dagmar (2021). Ex Vivo Infection of Human Skin with Herpes Simplex Virus 1 Reveals Mechanical Wounds as Insufficient Entry Portals via the Skin Surface. J. Virol., 95 (21). WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5514

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Abstract

Herpes simplex virus 1 (HSV-1) enters its human host via the skin and mucosa. The open question is how the virus invades this highly protective tissue in vivo to approach its receptors in the epidermis and initiate infection. Here, we per -formed ex vivo infection studies in human skin to investigate how susceptible the epidermis and dermis are to HSV-1 and whether wounding facilitates viral invasion. Upon ex vivo infection of complete skin, only sample edges with integrity loss dem-onstrated infected cells. After removal of the dermis, HSV-1 efficiently invaded the basal layer of the epidermis and, from there, gained access to suprabasal layers. This finding supports a high susceptibility of all epidermal layers which correlated with the surface expression of the receptors nectin-1 and herpesvirus entry mediator (HVEM). In contrast, only single infected cells were detected in the separated dermis, where minor expression of the receptors was found. Interestingly, after wounding, nearly no infection of the epidermis was observed via the skin surface. However, if the wounding of the skin samples led to breaks through the dermis, HSV-1 infected mainly keratinocytes via the damaged dermal layer. The application of latex beads revealed only occasional entry via the wounded dermis; however, it facilitated pene-tration via the wounded skin surface. Thus, we suggest that although the wounded human skin surface allows particle penetration, the skin still provides barriers that prevent HSV-1 from reaching its receptors. IMPORTANCE The human pathogen herpes simplex virus 1 (HSV-1) invades its host via the skin and mucosa, which leads to primary infection of the epithelium. As the various epithelial barriers effectively protect the tissue against viral invasion, success-ful infection most likely depends on tissue damage. We addressed the initial invasion process in human skin by ex vivo infection to understand how HSV-1 overcomes physical skin barriers and reaches its receptors to enter skin cells. Our results demon-strate that intact skin samples allow viral access only from the edges, while the epi-dermis is highly susceptible once the basal epidermal layer serves as an initial entry portal. Surprisingly, mechanical wounding did not facilitate HSV-1 entry via the skin surface, although latex beads still penetrated via the lesions. Our results imply that successful invasion of HSV-1 depends on how well the virus can reach its receptors, which was not accomplished by skin lesions under ex vivo conditions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code De la Cruz, Nydia C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Moeckel, Maureen UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Sunaoglu, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Malter, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Zinser, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Knebel-Moersdorf, Dagmar UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-561333
DOI:	10.1128/JVI.01338-21
Journal or Publication Title:	J. Virol.
Volume:	95
Number:	21
Date:	2021
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5514
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MURINE EPIDERMIS; TYPE-1; MEDIATOR Multiple languages Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56133