Moeckel, Maureen, de la Cruz, Nydia C., Ruebsam, Matthias, Wirtz, Lisa, Tantcheva-Poor, Iliana, Malter, Wolfram, Zinser, Max, Bieber, Thomas and Knebel-Moersdorf, Dagmar (2022). Herpes Simplex Virus 1 Can Bypass Impaired Epidermal Barriers upon Ex Vivo Infection of Skin from Atopic Dermatitis Patients. J. Virol., 96 (17). WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5514
Full text not available from this repository.Abstract
To infect its human host, herpes simplex virus 1 (HSV-1) must overcome the protective barriers of skin and mucosa. Here, we addressed whether pathological skin conditions can facilitate viral entry via the skin surface and used ex vivo infection studies to explore viral invasion in atopic dermatitis (AD) skin characterized by disturbed barrier functions. Our focus was on the visualization of the onset of infection in single cells to determine the primary entry portals in the epidermis. After ex vivo infection of lesional AD skin, we observed infected cells in suprabasal layers indicating successful invasion in the epidermis via the skin surface which was never detected in control skin where only sample edges allowed viral access. The redistribution of filaggrin, loricrin, and tight-junction components in the lesional skin samples suggested multiple defective mechanical barriers. To dissect the parameters that contribute to HSV-1 invasion, we induced an AD-like phenotype by adding the Th2 cytokines interleukin 4 (IL-4) and IL-13 to healthy human skin samples. Strikingly, we detected infected cells in the epidermis, implying that the IL-4/IL-13-driven inflammation is sufficient to induce modifications allowing HSV-1 to penetrate the skin surface. In summary, not only did lesional AD skin facilitate HSV-1 penetration but IL-4/IL-13 responses alone allowed virus invasion. Our results suggest that the defective epidermal barriers of AD skin and the inflammation-induced altered barriers in healthy skin can make receptors accessible for HSV-1. IMPORTANCE Herpes simplex virus 1 (HSV-1) can target skin to establish primary infection in the epithelium. While the human skin provides effective barriers against viral invasion under healthy conditions, a prominent example of successful invasion is the disseminated HSV-1 infection in the skin of atopic dermatitis (AD) patients. AD is characterized by impaired epidermal barrier functions, chronic inflammation, and dysbiosis of skin microbiota. We addressed the initial invasion process of HSV-1 in atopic dermatitis skin to understand whether the physical barrier functions are sufficiently disturbed to allow the virus to invade skin and reach its receptors on skin cells. Our results demonstrate that HSV-1 can indeed penetrate and initiate infection in atopic dermatitis skin. Since treatment of skin with IL-4 and IL-13 already resulted in successful invasion, we assume that inflammation-induced barrier defects play an important role for the facilitated access of HSV-1 to its target cells. Herpes simplex virus 1 (HSV-1) can target skin to establish primary infection in the epithelium. While the human skin provides effective barriers against viral invasion under healthy conditions, a prominent example of successful invasion is the disseminated HSV-1 infection in the skin of atopic dermatitis (AD) patients.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||
| Creators: |
|
||||||||||||||||||||||||||||||||||||||||
| URN: | urn:nbn:de:hbz:38-665298 | ||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1128/jvi.00864-22 | ||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | J. Virol. | ||||||||||||||||||||||||||||||||||||||||
| Volume: | 96 | ||||||||||||||||||||||||||||||||||||||||
| Number: | 17 | ||||||||||||||||||||||||||||||||||||||||
| Date: | 2022 | ||||||||||||||||||||||||||||||||||||||||
| Publisher: | AMER SOC MICROBIOLOGY | ||||||||||||||||||||||||||||||||||||||||
| Place of Publication: | WASHINGTON | ||||||||||||||||||||||||||||||||||||||||
| ISSN: | 1098-5514 | ||||||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||
| Uncontrolled Keywords: |
|
||||||||||||||||||||||||||||||||||||||||
| URI: | http://kups.ub.uni-koeln.de/id/eprint/66529 |
Downloads
Downloads per month over past year
Altmetric
Export
Actions (login required)
 |
View Item |