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Virological characterization of the 2022 outbreak-causing monkeypox virus using human keratinocytes and colon organoids

Watanabe, Yukio Kimura, Izumi Hashimoto, Rina Sakamoto, Ayaka Yasuhara, Naoko Yamamoto, Takuya Genotype to Phenotype Japan (GP-Japan) Consortium Sato, Kei Takayama, Kazuo 京都大学 DOI:10.1002/jmv.28827

2023.06

概要

The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids. We observed that MPXV infections, regardless of strain, caused cellular dysfunction and mitochondrial damage in keratinocytes. Notably, a significant increase in the expression of hypoxia-related genes was observed specifically in 2022 MPXV-infected keratinocytes. Our comparison of virological features between 2022 MPXV and prior endemic MPXV strains revealed signaling pathways potentially involved with the cellular damages caused by MPXV infections and highlights host vulnerabilities that could be utilized as protective therapeutic strategies against human mpox in the future.

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SUPP ORTING INFO RM ATION

Additional supporting information can be found online in the

Supporting Information section at the end of this article.

How to cite this article: Watanabe Y, Kimura I, Hashimoto R,

et al. Virological characterization of the 2022 outbreak‐

causing monkeypox virus using human keratinocytes and

colon organoids. J Med Virol. 2023;95:e28827.

doi:10.1002/jmv.28827

10969071, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jmv.28827 by Cochrane Japan, Wiley Online Library on [07/06/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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