Induction of angiogenic chemokine CCL2 by human herpesvirus 8 chemokine receptor.
Human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma (KS), an endothelial cell lesion believed to be initiated and driven primarily by cytokine dysregulation. Among the viral proteins suspected as contributing to viral pathogenesis is the lytically expressed viral G protein-coupled receptor (vGPCR), which can induce various cellular cytokines. CC ligand-2 (CCL2/MCP-1) is a vGPCR-regulated angiogenic chemokine found at elevated levels in KS lesions and induced by HHV-8 infection of endothelial cells. Here we show that vGPCR induces CCL2 in endothelial cells via activation of C/EBPbeta and that vGPCR and C/EBPbeta are critical components of CCL2 induction by HHV-8 infection of endothelial cultures. To our knowledge, this is the first report of vGPCR-mediated cytokine induction, and its characterization, in the context of virus infection. Our results identify a mechanism by which vGPCR can contribute, in a host cell shutoff-independent manner, to viral pathogenesis.
Choi
Young Bong
YB
Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Nicholas
John
J
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000821:virology; D019288:Herpesvirus 8, Human / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D019707:Receptors, Chemokine / Q000378:metabolism*
D022782:CCAAT-Enhancer-Binding Protein-beta; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C115448:G protein-coupled receptor, Human herpesvirus 8; D019707:Receptors, Chemokine