Cell host & microbe, 2011-12, Vol.10 (6), p.577-590
2011
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- Autor(en) / Beteiligte
- Titel
- KSHV-Initiated Notch Activation Leads to Membrane-Type-1 Matrix Metalloproteinase-Dependent Lymphatic Endothelial-to-Mesenchymal Transition
- Ist Teil von
- Cell host & microbe, 2011-12, Vol.10 (6), p.577-590
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2011
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- Kaposi sarcoma (KS), an angioproliferative disease associated with Kaposi sarcoma herpesvirus (KSHV) infection, harbors a diversity of cell types ranging from endothelial to mesenchymal cells of unclear origin. We developed a three-dimensional cell model for KSHV infection and used it to demonstrate that KSHV induces transcriptional reprogramming of lymphatic endothelial cells to mesenchymal cells via endothelial-to-mesenchymal transition (EndMT). KSHV-induced EndMT was initiated by the viral proteins vFLIP and vGPCR through Notch pathway activation, leading to gain of membrane-type-1 matrix metalloproteinase (MT1-MMP)-dependent invasive properties and concomitant changes in viral gene expression. Mesenchymal markers and MT1-MMP were found codistributed with a KSHV marker in the same cells from primary KS biopsies. Our data explain the heterogeneity of cell types within KS lesions and suggest that KSHV-induced EndMT may contribute to KS development by giving rise to infected, invasive cells while providing the virus a permissive cellular microenvironment for efficient spread. [Display omitted] ► KSHV induces mesenchymal reprogramming of lymphatic endothelial cells (LECs) in 3D ► KSHV-activated Notch-MT1-MMP axis regulates LEC reprogramming ► KSHV-reprogrammed LECs are invasive ► 3D microenvironment of infected LECs leads to viral gene expression changes
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1931-3128, 1934-6069eISSN: 1934-6069DOI: 10.1016/j.chom.2011.10.011Titel-ID: cdi_swepub_primary_oai_prod_swepub_kib_ki_se_123833443
- Format
- –
- Schlagworte
- Cell Line, Endothelial Cells - cytology, Endothelial Cells - enzymology, Endothelial Cells - virology, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Viral, Herpesvirus 8, Human - genetics, Herpesvirus 8, Human - physiology, Humans, Matrix Metalloproteinase 14 - metabolism, Medicin och hälsovetenskap, Mesenchymal Stem Cells - cytology, Mesenchymal Stem Cells - enzymology, Mesenchymal Stem Cells - virology, Receptors, Notch - metabolism, Sarcoma, Kaposi - enzymology, Sarcoma, Kaposi - metabolism, Sarcoma, Kaposi - physiopathology, Sarcoma, Kaposi - virology, Signal Transduction, Viral Proteins - genetics, Viral Proteins - metabolism