Mpox virus infection and drug treatment modelled in human skin organoids

Pengfei Li, Spyridon T. Pachis, Guige Xu, Rick Schraauwen, Roberto Incitti, Annemarie C. de Vries, Marco J. Bruno, Maikel P. Peppelenbosch, Intikhab Alam, Karine Raymond*, Qiuwei Pan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2067-2079
Number of pages13
JournalNature Microbiology
Volume8
Issue number11
Early online date12 Oct 2023
DOIs
Publication statusPublished - Nov 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.

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