دورية أكاديمية

KSHV infection of endothelial precursor cells with lymphatic characteristics as a novel model for translational Kaposi's sarcoma studies

التفاصيل البيبلوغرافية
العنوان: KSHV infection of endothelial precursor cells with lymphatic characteristics as a novel model for translational Kaposi's sarcoma studies
المؤلفون: Tuohinto, Krista, DiMaio, Terri P., Kiss, Elina, Laakkonen, Pirjo P., Saharinen, Pipsa, Karnezis, Tara P., Lagunoff, Michael, Ojala, Päivi M. P.
المساهمون: Research Programs Unit, CAN-PRO - Translational Cancer Medicine Program, STEMM - Stem Cells and Metabolism Research Program, Helsinki Institute of Life Science HiLIFE, Infra, Pirjo Maarit Laakkonen / Principal Investigator, Department of Biochemistry and Developmental Biology, Helsinki In Vivo Animal Imaging Platform (HAIP), Department of Pathology, Medicum
بيانات النشر: PUBLIC LIBRARY OF SCIENCE
سنة النشر: 2023
المجموعة: Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto
مصطلحات موضوعية: Progenitor cells, Herpesvirus-infection, Gene-expression, Spindle cells, Origin, Activation, Suggests, Program, Latency, Leads, 3111 Biomedicine, 11832 Microbiology and virology
الوصف: Author summaryKaposi's sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). The main proliferative component of KS, spindle cells, express markers of lymphatic and blood endothelium. Endothelial precursor cells, which are circulating endothelial colony forming cells (ECFCs), have been proposed as the source of spindle cells. Here we examined both blood and lymphatic ECFCs infected with KSHV. Lymphatic ECFCs are readily infected by KSHV, maintain the viral episomes and show modest transformation of the cells, which the infected blood ECFCs and all uninfected ECFCs failed to show. The lymphatic ECFCs express SOX18, which supported the maintenance of high copy numbers of KSHV genomes. The KSHV-infected lymphatic ECFCs persisted in vivo and recapitulated the phenotype of KS tumor cells such as high number of viral genome copies and spindling morphology. These KS tumor cell hallmarks were significantly reduced by SOX18 chemical inhibition using a small molecule SM4 treatment. These data suggest that KSHV-infected lymphatic ECFCs could be the progenitors of KS spindle cells and are a promising model for the translational studies to develop new therapies for KS.Kaposi's sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's 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 ...
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
العلاقة: Tuohinto , K , DiMaio , T P , Kiss , E , Laakkonen , P P , Saharinen , P , Karnezis , T P , Lagunoff , M & Ojala , P M P 2023 , ' KSHV infection of endothelial precursor cells with lymphatic characteristics as a novel model for translational Kaposi's sarcoma studies ' , PLoS Pathogens , vol. 19 , no. 1 , e1010753 . https://doi.org/10.1371/journal.ppat.1010753Test; ORCID: /0000-0002-9620-095X/work/130600073; 2c77889a-daae-4d48-9bbc-5db9a1ffe7f5; http://hdl.handle.net/10138/356008Test; 000935334400001
الإتاحة: http://hdl.handle.net/10138/356008Test
حقوق: cc_by ; openAccess ; info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.F2C879D
قاعدة البيانات: BASE