Krista Tuohinto, Matthew S Graus, Peyton Staab, Ville Tiusanen, Fei Liangru, Susav Pradhan, Yew Yan Wong, Simon Weissmann, Jieqiong Lou, Elizabeth Hinde, Justin Wong, Quintin Lee, Alexey Terskikh, Martin Alvarez-Kuglen, Tara Karnezis, Thomas Günther, Adam Grundhoff, Biswajyoti Sahu, Mathias Francoís, Päivi M Ojala
{"title":"致瘤病毒劫持SOX18前导功能以增强病毒持久性。","authors":"Krista Tuohinto, Matthew S Graus, Peyton Staab, Ville Tiusanen, Fei Liangru, Susav Pradhan, Yew Yan Wong, Simon Weissmann, Jieqiong Lou, Elizabeth Hinde, Justin Wong, Quintin Lee, Alexey Terskikh, Martin Alvarez-Kuglen, Tara Karnezis, Thomas Günther, Adam Grundhoff, Biswajyoti Sahu, Mathias Francoís, Päivi M Ojala","doi":"10.1101/2025.06.28.662102","DOIUrl":null,"url":null,"abstract":"<p><p>Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong oncogenic infection in lymphatic endothelial cells (LECs) by ensuring episomal maintenance of its genome via the viral protein LANA. Efficient viral genome maintenance typically involves host DNA replication and episome tethering, but the extent of cell-type-specific regulation remains unclear. Here, we identify that KSHV hijacks the pioneering function of the endothelial-specific transcription factor SOX18 to facilitate persistence of viral episomes. Upon infection, LANA co-opts SOX18 to recruit the SWI/SNF chromatin-remodeling complex via its ATPase subunit BRG1, enhancing chromatin accessibility and enabling efficient viral genome persistence. Disruption of SOX18 or BRG1-genetically or pharmacologically-leads to reduced episome load and attenuated hallmarks of virus infection. This work highlights how viruses can harness lineage-specific transcriptional regulators to establish persistent nuclear retention of their episome into the host genome.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236786/pdf/","citationCount":"0","resultStr":"{\"title\":\"Oncogenic virus hijacks SOX18 pioneer function to enhance viral persistence.\",\"authors\":\"Krista Tuohinto, Matthew S Graus, Peyton Staab, Ville Tiusanen, Fei Liangru, Susav Pradhan, Yew Yan Wong, Simon Weissmann, Jieqiong Lou, Elizabeth Hinde, Justin Wong, Quintin Lee, Alexey Terskikh, Martin Alvarez-Kuglen, Tara Karnezis, Thomas Günther, Adam Grundhoff, Biswajyoti Sahu, Mathias Francoís, Päivi M Ojala\",\"doi\":\"10.1101/2025.06.28.662102\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong oncogenic infection in lymphatic endothelial cells (LECs) by ensuring episomal maintenance of its genome via the viral protein LANA. Efficient viral genome maintenance typically involves host DNA replication and episome tethering, but the extent of cell-type-specific regulation remains unclear. Here, we identify that KSHV hijacks the pioneering function of the endothelial-specific transcription factor SOX18 to facilitate persistence of viral episomes. Upon infection, LANA co-opts SOX18 to recruit the SWI/SNF chromatin-remodeling complex via its ATPase subunit BRG1, enhancing chromatin accessibility and enabling efficient viral genome persistence. Disruption of SOX18 or BRG1-genetically or pharmacologically-leads to reduced episome load and attenuated hallmarks of virus infection. This work highlights how viruses can harness lineage-specific transcriptional regulators to establish persistent nuclear retention of their episome into the host genome.</p>\",\"PeriodicalId\":519960,\"journal\":{\"name\":\"bioRxiv : the preprint server for biology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236786/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv : the preprint server for biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2025.06.28.662102\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv : the preprint server for biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2025.06.28.662102","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Oncogenic virus hijacks SOX18 pioneer function to enhance viral persistence.
Kaposi's sarcoma herpesvirus (KSHV) establishes lifelong oncogenic infection in lymphatic endothelial cells (LECs) by ensuring episomal maintenance of its genome via the viral protein LANA. Efficient viral genome maintenance typically involves host DNA replication and episome tethering, but the extent of cell-type-specific regulation remains unclear. Here, we identify that KSHV hijacks the pioneering function of the endothelial-specific transcription factor SOX18 to facilitate persistence of viral episomes. Upon infection, LANA co-opts SOX18 to recruit the SWI/SNF chromatin-remodeling complex via its ATPase subunit BRG1, enhancing chromatin accessibility and enabling efficient viral genome persistence. Disruption of SOX18 or BRG1-genetically or pharmacologically-leads to reduced episome load and attenuated hallmarks of virus infection. This work highlights how viruses can harness lineage-specific transcriptional regulators to establish persistent nuclear retention of their episome into the host genome.
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