Kaposi's sarcoma-associated herpesvirus infection of blood endothelial cells induces lymphatic differentiation.
Kaposi's sarcoma-associated herpesvirus (KSHV) is necessary for KS, a highly vascularized tumor predominated by endothelial-derived spindle cells that express markers of lymphatic endothelium. Following KSHV infection of TIME cells, an immortalized human dermal microvascular endothelial cell (DMVEC) line, expression of many genes specific to lymphatic endothelium, including VEGFR3, podoplanin, LYVE-1, and Prox-1, is significantly increased. Increases in VEGFR3 and podoplanin protein are also demonstrated following latent infection. Examination of cytokine secretion showed that KSHV infection significantly induces hIL-6 while strongly inhibiting secretion of IL-8, a gene product that is decreased by differentiation of blood to lymphatic endothelial cells. These studies support the hypotheses that latent KSHV infection of blood endothelial cells drives their differentiation to lymphatic endothelial cells.
Carroll
Patrick A
PA
Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Brazeau
Elizabeth
E
Lagunoff
Michael
M
D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002460:Cell Line; D002472:Cell Transformation, Viral; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis / Q000235:genetics; D033921:Vesicular Transport Proteins; D017735:Virus Latency; D000098551:Prospero-Related Homeobox 1 Protein; D000098853:Podoplanin
D015415:Biomarkers; D006023:Glycoproteins; D018398:Homeodomain Proteins; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D040321:Vascular Endothelial Growth Factor Receptor-3; D033921:Vesicular Transport Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C119248:LYVE1 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin