{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:31:45Z","timestamp":1783531905455,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"crossref","award":["22wm0325014h0003"],"award-info":[{"award-number":["22wm0325014h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"crossref","award":["25wm0325057h0003"],"award-info":[{"award-number":["25wm0325057h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["23K08839"],"award-info":[{"award-number":["23K08839"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED","award":["JP18am0101102"],"award-info":[{"award-number":["JP18am0101102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human papillomavirus (HPV) infection is a primary driver of cervical cancer. Integration of HPV into the human genome causes persistent expression of viral oncogenes E6 and E7, which promote carcinogenesis and disrupt host genomic function. However, the impact of integration on host gene expression remains incompletely understood. We used multimodal RNA sequencing, combining total RNA-seq and Cap Analysis of Gene Expression (CAGE), to clarify virus\u2013host interactions after HPV integration. HPV-derived transcripts were detected in 17 of 20 clinical samples. In most specimens, transcriptional start sites (TSSs) showed predominant early promoter usage, and transcript patterns differed with detectable E4 RNA region. Notably, the high RNA expressions of E4 region and viral-human chimeric RNAs were mutually exclusive. Chimeric RNAs were identified in 13 of 17 samples, revealing 16 viral integration sites (ISs). CAGE data revealed two patterns of TSS upregulation centered on the ISs: a two-sided pattern (43.8%) and a one-sided pattern (31.3%). Total RNA-seq showed upregulation of 12 putative cancer-related genes near ISs, including MAGI1-AS1, HAS3, CASC8, BIRC2, and MMP12. These findings indicate that HPV integration drives transcriptional activation near ISs, enhancing expression of adjacent oncogenes. Our study deepens understanding of HPV-induced carcinogenesis and informs precision medicine strategies for cervical cancer.<\/jats:p>","DOI":"10.3390\/v17101344","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T13:33:41Z","timestamp":1759757621000},"page":"1344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elucidating Alterations in Viral and Human Gene Expression Due to Human Papillomavirus Integration by Using Multimodal RNA Sequencing"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3863-0701","authenticated-orcid":false,"given":"Kana","family":"Tamai","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonoko","family":"Kinjo","sequence":"additional","affiliation":[{"name":"National Institute of Genetics, Mishima 411-0801, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo 113-8655, Japan"},{"name":"Laboratory of Human Single Cell Immunology, World Premier International Immunology, Frontier Research Center, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0696-5175","authenticated-orcid":false,"given":"Kazunori","family":"Nagasaka","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Teikyo University, Itabashi 173-8606, 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2278-3443","authenticated-orcid":false,"given":"Hitoshi","family":"Iuchi","sequence":"additional","affiliation":[{"name":"Waseda Research Institute for Science and Engineering, Waseda University, Shinjuku 169-8555, Japan"},{"name":"Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), National Institute of Advanced Industrial Science and Technology, Shinjuku 169-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4545-0569","authenticated-orcid":false,"given":"Mayuyo","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7218-6401","authenticated-orcid":false,"given":"Kenbun","family":"Sone","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9466-1034","authenticated-orcid":false,"given":"Michiaki","family":"Hamada","sequence":"additional","affiliation":[{"name":"Waseda Research Institute for Science and Engineering, Waseda University, Shinjuku 169-8555, Japan"},{"name":"Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), National Institute of Advanced Industrial Science and Technology, Shinjuku 169-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Kawana","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and 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