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However, the infection profile of MPXV in testicular tissue\u2010associated cells and the host immune response remain poorly understood. This study investigated the susceptibility of Sertoli cells, which serve as the structural and functional core unit of seminiferous tubules in the testis, to MPXV, and the host gene expression profiles were analyzed. Following MPXV inoculation of Sertoli cells, viral load detection, transmission electron microscopy, and transcriptomic sequencing revealed that MPXV induces lesions in Sertoli cells, accompanied by viral replication. The virus assembles and replicates by forming viral factories within the cytoplasm, ultimately releasing enveloped viral particles via exocytosis. Upon infection, genes involved in stress response, inflammation pathways, and cell cycle regulation are upregulated. Additionally, genes associated with olfactory transduction pathways are activated, while antiviral genes are suppressed, and virus\u2010related genes linked to interferon receptors are highly expressed. This study demonstrates that MPXV infects human Sertoli cells and defines the accompanying host\u2010response landscape, offering cell\u2010level mechanistic clues that may be relevant to the rare occurrence of epididymo\u2010orchitis in severe MPXV cases and guiding hypothesis\u2010driven in\u2010vivo validation.<\/jats:p>","DOI":"10.1002\/jmv.70661","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T20:19:04Z","timestamp":1762201144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of Human Sertoli Cells Infected With Monkeypox Virus"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5428-3080","authenticated-orcid":false,"given":"Yongyang","family":"Sun","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key 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