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dc.contributor.authorDubich, Tatyana
dc.contributor.authorDittrich, Anne
dc.contributor.authorBousset, Kristine
dc.contributor.authorGeffers, Robert
dc.contributor.authorBüsche, Guntram
dc.contributor.authorKöster, Mario
dc.contributor.authorHauser, Hansjörg
dc.contributor.authorSchulz, Thomas F
dc.contributor.authorWirth, Dagmar
dc.identifier.citationJ Mol Med (Berl). 2021 Jan 23. doi: 10.1007/s00109-020-02020-8. Epub ahead of print.en_US
dc.description.abstractKaposi's sarcoma-associated herpesvirus (KSHV) is a human tumorigenic virus and the etiological agent of an endothelial tumor (Kaposi's sarcoma) and two B cell proliferative diseases (primary effusion lymphoma and multicentric Castleman's disease). While in patients with late stage of Kaposi's sarcoma the majority of spindle cells are KSHV-infected, viral copies are rapidly lost in vitro, both upon culture of tumor-derived cells or from newly infected endothelial cells. We addressed this discrepancy by investigating a KSHV-infected endothelial cell line in various culture conditions and in tumors of xenografted mice. We show that, in contrast to two-dimensional endothelial cell cultures, KSHV genomes are maintained under 3D cell culture conditions and in vivo. Additionally, an increased rate of newly infected cells was detected in 3D cell culture. Furthermore, we show that the PI3K/Akt/mTOR and ATM/γH2AX pathways are modulated and support an improved KSHV persistence in 3D cell culture. These mechanisms may contribute to the persistence of KSHV in tumor tissue in vivo and provide a novel target for KS specific therapeutic interventions. KEY MESSAGES: In vivo maintenance of episomal KSHV can be mimicked in 3D spheroid cultures 3D maintenance of KSHV is associated with an increased de novo infection frequency PI3K/Akt/mTOR and ATM/ γH2AX pathways contribute to viral maintenance.en_US
dc.publisherSpringer Internationalen_US
dc.rightsAttribution 4.0 International*
dc.subject3D cultureen_US
dc.subjectEpisomal viral genomesen_US
dc.subjectKSHV infected endothelial cellsen_US
dc.subjectViral maintenanceen_US
dc.subjectXenograft modelen_US
dc.title3D culture conditions support Kaposi's sarcoma herpesvirus (KSHV) maintenance and viral spread in endothelial cells.en_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalJournal of molecular medicine (Berlin, Germany)en_US
dc.source.journaltitleJournal of molecular medicine (Berlin, Germany)

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Attribution 4.0 International
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