Modulation of host gene expression by the constitutively active G protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus.
Kaposi's sarcoma-associated herpes virus (KSHV) infects B cells and microvascular endothelium,and is linked to both lymphoid and endothelial neoplasms. KSHV encodes a G protein-coupled receptor (v-GPCR) that can bind several CC and CXC chemokines but is able to signal in the absence of known ligands. This signaling can transform cultured fibroblasts, promote angiogenesis in vitro and in vivo, and activate the mitogen-activated protein kinase, c-Jun-NH(2)-terminal kinase, and p38 pathways. To assess the potential impact of v-GPCR signaling on host cell biology we have examined cellular gene expression in v-GPCR-transfected cells using DNA microarrays. v-GPCR expression up-regulated numerous cellular transcripts in both BJAB B cells and SLK endothelial cells, but with a remarkable degree of cell-type specificity. Among the most highly regulated genes in endothelial cells were the cytokines interleukin 6 and GRO alpha; several genes affecting endothelial/vascular growth and remodeling were also induced, including plasminogen, thrombomodulin, the urokinase-type plasminogen activator receptor, and to a modest extent vascular endothelial growth factor C. By contrast, the most highly regulated genes in B cells were the CC chemokines macrophage inflammatory protein 1 alpha and macrophage inflammatory protein 1 beta. No genes other than members of the dual-specificity phosphatase family were induced in both cell lines. The results indicate that the effects of KSHV GPCR expression in these two target cell types differ considerably and suggest that signaling by this molecule may make different contributions to the pathogenesis of KSHV-related endothelial and lymphoproliferative lesions.
Polson
Andrew G
AG
Department of Microbiology and Immunology, University of California, San Francisco, California 94143-0414, USA.
Wang
David
D
DeRisi
Joseph
J
Ganem
Don
D
D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology / Q000821:virology; D005786:Gene Expression Regulation / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
C115448:G protein-coupled receptor, Human herpesvirus 8; D019707:Receptors, Chemokine; D014764:Viral Proteins