Mpox virus infection and drug treatment modelled in human skin organoids
Open accessAbstract
Mpox virus (MPXV) primarily infects human skin to cause lesions. Currently, robust models that recapitulate skin infection by MPXV are lacking. Here we demonstrate that human induced pluripotent stem cell-derived skin organoids are susceptible to MPXV infection and support infectious virus production. Keratinocytes, the predominant cell type of the skin epithelium, effectively support MPXV infection. Using transmission electron microscopy, we visualized the four stages of intracellular virus particle assembly: crescent formation, immature virions, mature virions and wrapped virions. Transcriptional analysis showed that MPXV infection rewires the host transcriptome and triggers abundant expression of viral transcripts. Early treatment with the antiviral drug tecovirimat effectively inhibits infectious virus production and prevents host transcriptome rewiring. Delayed treatment with tecovirimat also inhibits infectious MPXV particle production, albeit to a lesser extent. This study establishes human skin organoids as a robust experimental model for studying MPXV infection, mapping virus-host interactions and testing therapeutics.
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hiPSC-derived skin organoids have hair follicles, pigmentation, dermal stratification, appendage patterning, and innervation.
“Recent advances in human induced pluripotent stem cell (hiPSC) technology have enabled the generation of skin organoids (SKO) with hair follicles, pigmentation, dermal stratification, appendage patterning, and innervation.[ 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [29]
The paper’s introductory section describes hiPSC-derived skin organoids with multilayer structure, hair follicles, and sebaceous glands; Skin organoid generation also describes producing hair-bearing organoids. Our copy does not establish pigmentation, appendage patterning, or innervation, so it supports only part of the cited list. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPrevious human SKO models were devoid of vascularization and immune cells.
“Previous human SKO models were devoid of vascularization and immune cells.[ 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 59 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [29]
The Discussion states that immune cells are currently lacking in the authors’ skin organoids, supporting that part of the claim. Our copy does not establish that these or previous human skin organoid models lacked vascularization; a search for vascularization and blood vessels found no supporting passage. (LLM, conf=0.85)
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Cites
Hair-bearing human skin generated entirely from pluripotent stem cells
Lee, J., Rabbani, C. C., Gao, H., Steinhart, M. R., Woodruff, B. M., Pflum, Z. E., Kim, A., Heller, S., Liu, Y., Shipchandler, T. Z., et al. (2020) · Nature · doi:10.1038/s41586-020-2352-3 · Cited by 487 · cited 3× · see citing works
“They also bear multiple appendages such as hair follicles and sebaceous glands 11 .”
BackgroundMethodCharacterization of the epidermal-dermal junction in hiPSC-derived skin organoids
Ramovs, V., Janssen, H., Fuentes, I., Pitaval, A., Rachidi, W., Chuva de Sousa Lopes, S. M., Freund, C., Gidrol, X., Mummery, C. L., & Raymond, K. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.04.008 · Cited by 44 · see citing works
Self-citationApplication of an iPSC‐Derived Organoid Model for Localized Scleroderma Therapy
Ma, J., Li, W., Cao, R., Gao, D., Zhang, Q., Li, X., Li, B., Lv, L., Li, M., Jiang, J., et al. (2022) · Advanced Science · doi:10.1002/advs.202106075 · Cited by 38 · cited 1× · see citing works
“Collectively, these features endow skin organoids with unique advantages for studying skin-associated diseases, microbial infection and drug development 13,14 .”
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Flagged first, then by citations
Research works printed but not linked: 4
- [17]17. Weisberg, A. S. et al. Enigmatic origin of the poxvirus membrane from the endoplasmic reticulum shown by 3D imaging of vaccinia virus assembly mutants. Proc. Natl Acad. Sci. USA 114 , E11001-E11009 (2017).
- [18]18. Yang, Z., Bruno, D. P., Martens, C. A., Porcella, S. F. & Moss, B. Simultaneous high-resolution analysis of vaccinia virus and host cell transcriptomes by deep RNA sequencing. Proc. Natl Acad. Sci. USA 107 , 11513-11518 (2010).
- [24]24. Gupta, A. K., Talukder, M., Rosen, T. & Piguet, V. Differential diagnosis, prevention, and treatment of mpox (Monkeypox): a review for dermatologists. Am. J. Clin. Dermatol. 24 , 541-556 (2023).
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Cited by
Sorted by citations
Mostina, M., Sun, J., Sim, S. L., Ahmed, I. A., Souza‐Fonesca‐Guimaraes, F., Wolvetang, E. J., Brown, J., Kumari, S., Khosrotehrani, K., & Shafiee, A. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202502108 · Cited by 17 · see citing works
- Authors
- Li, P., Pachis, S. T., Xu, G., Schraauwen, R., Incitti, R., de Vries, A. C., Bruno, M. J., Peppelenbosch, M. P., Alam, I., Raymond, K., & Pan, Q.
- Affiliations
- Erasmus MC (NL)
- Leiden University Medical Center (NL)
- King Abdullah University of Science and Technology (SA)
- Inserm (FR)
- Corresponding author
- Raymond, Karine
- Pan, Qiuwei
- ORCID
- Venue
- Nature Microbiology
- Published
- 2023-10-12
- Volume
- 8
- Issue
- 11
- Pages
- 2067-2079
- ISSN
- 2058-5276 (ISSN-L)
- OpenAlex
- W4387580053
- Cited by
- 77
- References
- 3
- Citations by year
- 2026: 22 · 2025: 29 · 2024: 24 · 2023: 2
- FWCI
- 10.12
- Type
- journal article
- Language
- en
- Open access
- green
- pure.eur.nl
- Licence
- Locations
- Nature Microbiology (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- HAL (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (91719300)
- Novo Nordisk Fonden (NNF21CC0073729)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Poxvirus research and outbreaks
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Keywords
- monkeypox virus, skin organoids, keratinocytes, host-virus interaction, viral assembly, tecovirimat, antiviral drug testing, host transcriptome, infectious virus production
- MeSH terms
- Humans, Monkeypox virus, Organoids, Mpox, Monkeypox, Mpox (monkeypox), Induced Pluripotent Stem Cells
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