Journal
VIROLOGY
Volume 328, Issue 1, Pages 7-18Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2004.07.008
Keywords
KSHV; HHV-8; endothelial; lymphatic; human herpesvirus; angiogenesis; VEGF receptor3; IL-6; podoplanin; Kaposi's sarcoma
Categories
Funding
- NCI NIH HHS [T32-CA09229, R01 CA097934, R01 CA097934-03, 1R01CA97934-01A1, T32 CA009229] Funding Source: Medline
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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, (C) 2004 Elsevier Inc. All rights reserved.
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