Complex Human Hair Bearing Skin Organoids as Model for Herpes Simplex Virus 1 Infection in the Skin

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Publié dans:bioRxiv (Feb 11, 2025)
Auteur principal: Wyler, Emanuel
Autres auteurs: Albertini, Silvia, Friedel, Caroline C, Manukyan, Artür, Huang, Jiabin, Krasemann, Susann, Plumbon, Izabela, Altmüller, Janine, Conrad, Thomas, Radbruch, Helena, Wali Hafezi, Hansen, Arne, Grundhoff, Adam, Landthaler, Markus, Fischer, Nicole, Czech-Sioli, Manja
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Cold Spring Harbor Laboratory Press
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MARC

LEADER 00000nab a2200000uu 4500
001 3165537713
003 UK-CbPIL
022 |a 2692-8205 
024 7 |a 10.1101/2025.02.10.637415  |2 doi 
035 |a 3165537713 
045 0 |b d20250211 
100 1 |a Wyler, Emanuel 
245 1 |a Complex Human Hair Bearing Skin Organoids as Model for Herpes Simplex Virus 1 Infection in the Skin 
260 |b Cold Spring Harbor Laboratory Press  |c Feb 11, 2025 
513 |a Working Paper 
520 3 |a 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.Competing Interest StatementThe authors have declared no competing interest. 
653 |a Infections 
653 |a Organoids 
653 |a Latent infection 
653 |a Keratinocytes 
653 |a Pluripotency 
653 |a Herpes simplex 
653 |a Cell culture 
653 |a Cell lines 
653 |a Herpes viruses 
653 |a Follicles 
653 |a Skin diseases 
653 |a Transcriptomics 
653 |a Viruses 
653 |a Latency 
653 |a Viral infections 
653 |a Paracrine signalling 
653 |a Nervous system 
653 |a Animal models 
653 |a Herpes labialis 
653 |a Epidermis 
700 1 |a Albertini, Silvia 
700 1 |a Friedel, Caroline C 
700 1 |a Manukyan, Artür 
700 1 |a Huang, Jiabin 
700 1 |a Krasemann, Susann 
700 1 |a Plumbon, Izabela 
700 1 |a Altmüller, Janine 
700 1 |a Conrad, Thomas 
700 1 |a Radbruch, Helena 
700 1 |a Wali Hafezi 
700 1 |a Hansen, Arne 
700 1 |a Grundhoff, Adam 
700 1 |a Landthaler, Markus 
700 1 |a Fischer, Nicole 
700 1 |a Czech-Sioli, Manja 
773 0 |t bioRxiv  |g (Feb 11, 2025) 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3165537713/abstract/embedded/75I98GEZK8WCJMPQ?source=fedsrch 
856 4 0 |3 Full text outside of ProQuest  |u https://www.biorxiv.org/content/10.1101/2025.02.10.637415v1