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| Item Type: | Preprint |
|---|---|
| Title: | Complex human hair bearing skin organoids as model for herpes simplex virus 1 infection in the skin |
| Creators Name: | Wyler, E., Albertini, S., Friedel, C.C., Manukyan, A., Huang, J., Krasemann, S., Plumbon, I., Altmüller, J., Conrad, T., Radbruch, H., Hafezi, W., Hansen, A., Grundhoff, A., Landthaler, M., Fischer, N. and Czech-Sioli, M. |
| Abstract: | For herpes simplex virus 1 (HSV-1) the skin is the primary site of infection. After the primary lytic infection, the virus enters the peripheral nervous system where it establishes latency. Spontaneous reactivation from the latently infected neurons leads to the typical HSV-1-induced diseases like cold sores. Modelling HSV-1-induced skin pathologies is challenging due to the variety of different cell types and structures in the skin and human-specific responses to the infection. Nevertheless, studies using monolayer cell lines, raft cultures, ex vivo skin and mouse models provided an immense contribution to our understanding of HSV-1 infection in the skin. However, the contribution of many skin-specific structures, especially hair follicles, to primary infection and reactivation remains unclear. In this study, we used complex human hair bearing skin organoids that were derived from induced pluripotent stem cell as a model for HSV-1 infection. We performed microscopy, bulk and spatial transcriptomics with single cell resolution to gain new insights into the cell-type specific viral life cycle and host responses. We show a restricted viral infection in keratinocytes of the epidermis and specific cell types of hair follicles. We show a cell type specific induction of interferon-stimulated genes and the TNF pathway. We can follow paracrine signaling through the tissue, showing that TNF response genes are upregulated in adjacent cells. Taken together, the skin organoids in combination with novel spatial transcriptomics techniques provide a physiologically highly relevant model system for HSV-1 infection in the skin. |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2025.02.10.637415 |
| Date: | 11 February 2025 |
| Official Publication: | https://doi.org/10.1101/2025.02.10.637415 |
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