TY - JOUR
KW - infection
KW - Pox virus
AU - Pengfei Li
AU - Spyridon T. Pachis
AU - Guige Xu
AU - Rick Schraauwen
AU - Roberto Incitti
AU - Annemarie C. de Vries
AU - Marco J. Bruno
AU - Maikel P. Peppelenbosch
AU - Intikhab Alam
AU - Karine Raymond
AU - Qiuwei Pan
AB - 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.
BT - Nature Microbiology
DA - 2023-10-12
DO - 10.1038/s41564-023-01489-6
LA - en
N2 - 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.
PY - 2023
SP - 1
EP - 13
T2 - Nature Microbiology
TI - Mpox virus infection and drug treatment modelled in human skin organoids
UR - https://www.nature.com/articles/s41564-023-01489-6
Y2 - 2023-10-13
SN - 2058-5276
ER -