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While HCMV expresses several microRNAs (miRNAs) during infection, their roles in NPC infection are unclear. Here, we characterized expression of cellular and viral miRNAs in HCMV\u2010infected NPCs during early infection by microarray and identified seven differentially expressed cellular miRNAs and six significantly upregulated HCMV miRNAs. Deep learning approaches were used to identify potential targets of significantly upregulated HCMV miRNAs against differentially expressed cellular messenger RNA\u00a0(mRNAs), and the associations with miRNA\u2010mRNA expression changes were observed. Gene ontology enrichment analysis indicated cellular gene targets were significantly enriched in pathways involved in neurodevelopment and cell\u2010cycle processes. Viral modulation of selected miRNAs and cellular gene targets involved in neurodevelopmental processes were further validated by real\u2010time quantitative reverse transcription polymerase chain reaction. Finally, a predicted 3\u2032 untranslated\u00a0region\u00a0target site of hcmv\u2010miR\u2010US25\u20101 in Jag1, a factor important for neurogenesis, was confirmed by mutagenesis. Reduction of Jag1 RNA and protein levels in NPCs was observed in response to transient expression of hcmv\u2010miR\u2010US25\u20101. A hcmv\u2010miR\u2010US25\u20101 mutant virus (\u0394miR\u2010US25) displayed limited ability to downregulate Jag1 mRNA levels and protein levels during the early infection stage compared with the wild type virus. Our collective experimental and computational investigation of miRNAs and cellular mRNAs expression in HCMV\u2010infected NPCs yields new insights into the roles of viral miRNAs in regulating NPC fate and their contributions to HCMV neuropathogenesis.<\/jats:p>","DOI":"10.1002\/jmv.28574","type":"journal-article","created":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T09:24:49Z","timestamp":1676107489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Human cytomegalovirus infection perturbs neural progenitor cell fate via the expression of viral microRNAs"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2749-7304","authenticated-orcid":false,"given":"Xuan","family":"Jiang","sequence":"first","affiliation":[{"name":"Guangzhou Institute of Pediatrics Guangzhou Women and Children Medical Center Guangdong China"},{"name":"Department of Medical Genetics, Oslo University 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