{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:58:47Z","timestamp":1784901527634,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010753","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Doctoral Program in Biomedicine, University of Helsinki"},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"crossref","award":["308663"],"award-info":[{"award-number":["308663"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Gertrude Biomedical Pty Ltd"},{"DOI":"10.13039\/100000054","name":"National cancer institute of the NIH","doi-asserted-by":"crossref","award":["RO1CA240479 and RO1097934"],"award-info":[{"award-number":["RO1CA240479 and RO1097934"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Gertrude Biomedical Pty Ltd"},{"name":"Finnish Cancer Foundation"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Kaposi\u2019s sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi\u2019s sarcoma (KS), a hyperplasia consisting of enlarged malformed vasculature and spindle-shaped cells, the main proliferative component of KS. While spindle cells express markers of lymphatic and blood endothelium, the origin of spindle cells is unknown. Endothelial precursor cells have been proposed as the source of spindle cells. We previously identified two types of circulating endothelial colony forming cells (ECFCs), ones that expressed markers of blood endothelium and ones that expressed markers of lymphatic endothelium. Here we examined both blood and lymphatic ECFCs infected with KSHV. Lymphatic ECFCs are significantly more susceptible to KSHV infection than the blood ECFCs and maintain the viral episomes during passage in culture while the blood ECFCs lose the viral episome. Only the KSHV-infected lymphatic ECFCs (K-ECFCLY) grew to small multicellular colonies in soft agar whereas the infected blood ECFCs and all uninfected ECFCs failed to proliferate. The K-ECFCLYs express high levels of SOX18, which supported the maintenance of high copy number of KSHV genomes. When implanted subcutaneously into NSG mice, the K-ECFCLYs persisted in vivo and recapitulated the phenotype of KS tumor cells with high number of viral genome copies and spindling morphology. These spindle cell hallmarks were significantly reduced when mice were treated with SOX18 inhibitor, SM4. These data suggest that KSHV-infected lymphatic ECFCs can be utilized as a KSHV infection model for in vivo translational studies to test novel inhibitors representing potential treatment modalities for KS.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010753","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T13:43:41Z","timestamp":1674481421000},"page":"e1010753","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["KSHV infection of endothelial precursor cells with lymphatic characteristics as a novel model for translational Kaposi\u2019s sarcoma studies"],"prefix":"10.1371","volume":"19","author":[{"given":"Krista","family":"Tuohinto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terri A.","family":"DiMaio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina A.","family":"Kiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirjo","family":"Laakkonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pipsa","family":"Saharinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Karnezis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5840-6175","authenticated-orcid":true,"given":"Michael","family":"Lagunoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-1832","authenticated-orcid":true,"given":"P\u00e4ivi M.","family":"Ojala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"issue":"8","key":"ppat.1010753.ref001","first-page":"1599","article-title":"Lymphatic endothelium and Kaposi\u2019s sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3","volume":"58","author":"L Jussila","year":"1998","journal-title":"Cancer Res"},{"issue":"6","key":"ppat.1010753.ref002","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1046\/j.1523-1747.1999.00798.x","article-title":"Vascular Endothelial Growth Factor-C (VEGF-C) and its Receptors KDR and flt-4 are Expressed in AIDS-Associated Kaposi\u2019s Sarcoma","volume":"113","author":"M Skobe","year":"1999","journal-title":"J. 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