Mpox virus infection and drug treatment modelled in human skin organoids.

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.

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. (2023). Mpox virus infection and drug treatment modelled in human skin organoids. Nature Microbiology.

We thank our colleagues at the hiPSC Hotel, Leiden University Medical Center, for providing hiPS cell lines. This work was supported by a VIDI grant (grant number 91719300) from the Dutch Research Council (NWO) to Q.P., and by the Novo Nordisk Foundation Center for Stem Cell Medicine supported by the Novo Nordisk Foundation, Denmark (grant number NNF21CC0073729) to K.R. K.R. is Chargé de Recherche at the Institut National de la Santé et de la Recherche Médicale (INSERM).

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