scholarly journals The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor: Lessons on dysregulated angiogenesis from a viral oncogene

2010 ◽  
pp. n/a-n/a ◽  
Author(s):  
Bruno C. Jham ◽  
Silvia Montaner
Keyword(s):  
G Protein ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
G Protein Coupled Receptor ◽  
Viral Oncogene ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
G Protein Coupled

G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator

Nature ◽  
10.1038/32472 ◽  
1998 ◽  
Vol 392 (6672) ◽  
pp. 210-210 ◽  
Author(s):  
Carlos Bais ◽  
Bianca Santomasso ◽  
Omar Coso ◽  
Leandros Arvanitakis ◽  
Elizabeth Geras Raaka ◽  
...  
Keyword(s):  
G Protein ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
G Protein Coupled Receptor ◽  
Viral Oncogene ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
G Protein Coupled

G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator

Nature ◽  
10.1038/34193 ◽  
1998 ◽  
Vol 391 (6662) ◽  
pp. 86-89 ◽  
Author(s):  
Carlos Bais ◽  
Bianca Santomasso ◽  
Omar Coso ◽  
Leandros Arvanitakis ◽  
Elizabeth Geras Raaka ◽  
...  
Keyword(s):  
G Protein ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
G Protein Coupled Receptor ◽  
Viral Oncogene ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
G Protein Coupled

scholarly journals The Kaposi's Sarcoma-Associated Herpesvirus G Protein-Coupled Receptor Has Broad Signaling Effects in Primary Effusion Lymphoma Cells

2003 ◽  
Vol 77 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Mark Cannon ◽  
Nicola J. Philpott ◽  
Ethel Cesarman
Keyword(s):  
G Protein ◽  
Kaposi's Sarcoma ◽  
Primary Effusion Lymphoma ◽  
Cell Cycle Control ◽  
Human Herpesvirus ◽  
Kaposi’S Sarcoma ◽  
G Protein Coupled Receptor ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
G Protein Coupled

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8 [HHV-8]) is a gamma-2-herpesvirus responsible for Kaposi's sarcoma as well as primary effusion lymphoma (PEL). KSHV is a lymphotropic virus that has pirated many mammalian genes involved in inflammation, cell cycle control, and angiogenesis. Among these is the early lytic viral G protein-coupled receptor (vGPCR), a homologue of the human interleukin-8 (IL-8) receptor. When expressed, vGPCR is constitutively active and can signal via mitogen- and stress-activated kinases. In certain models it activates the transcriptional potential of NF-κB and activator protein 1 (AP-1) and induces vascular endothelial growth factor (VEGF) production. Despite its importance to the pathogenesis of all KSHV-mediated disease, little is known about vGPCR activity in hematopoietic cells. To study the signaling potential and downstream effects of vGPCR in such cells, we have developed PEL cell lines that express vGPCR under the control of an inducible promoter. The sequences required for tetracycline-mediated induction were cloned into a plasmid containing adeno-associated virus type 2 elements to enhance integration efficiency. This novel plasmid permitted studies of vGPCR activity in naturally infected KSHV-positive lymphocytes. We show that vGPCR activates ERK-2 and p38 in PEL cells. In addition, it increases the transcription of reporter genes under the control of AP-1, NF-κB, CREB, and NFAT, a Ca2+-dependent transcription factor important to KSHV lytic gene expression. vGPCR also increases the transcription of KSHV open reading frames 50 and 57, thereby displaying broad potential to affect viral transcription patterns. Finally, vGPCR signaling results in increased PEL cell elaboration of KSHV vIL-6 and VEGF, two growth factors involved in KSHV-mediated disease pathogenesis.

scholarly journals Quantitative Analysis of the Bidirectional Viral G-Protein-Coupled Receptor and Lytic Latency-Associated Nuclear Antigen Promoter of Kaposi's Sarcoma-Associated Herpesvirus

2012 ◽  
Vol 86 (18) ◽  
pp. 9683-9695 ◽  
Author(s):  
Isaac B. Hilton ◽  
Dirk P. Dittmer
Keyword(s):  
Quantitative Analysis ◽  
G Protein ◽  
Binding Sites ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Nuclear Antigen ◽  
G Protein Coupled Receptor ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus ◽  
G Protein Coupled

Kaposi's sarcoma-associated herpesvirus (KSHV) establishes sustained latent persistence in susceptible cells. This is dependent on the latency-associated nuclear antigen (LANA). Understanding how LANA transcription is regulated thus aids our fundamental understanding of KSHV biology. Two hundred ninety-four base pairs are sufficient to regulate LANA transcription in response to the viral RTA protein and RBPjκ. The same region controls K14/viral G-protein-coupled receptor (vGPCR) transcription in the opposite direction. We used a quantitative analysis in conjunction with specific nucleotide substitutions and defined gain-of-function and loss-of-function RTA mutants to dissect this region. We used a bidirectional reporter driving red and green luciferase to study the LANApi and K14p promoters simultaneously. This established that LANApi/K14p functions as a canonical bidirectional promoter. Both were TATA dependent. K14p was favored by ∼50-fold in this context. Eliminating the distal LANApi TATA box increased maximal output and lowered the induction threshold (T) of K14p even further. Two RBPjκ binding sites were independently required; however, at high concentrations of RTA, direct interactions with an RTA-responsive element (RRE) could complement the loss of one RBPjκ binding site. Intracellular Notch (ICN) was no longer able to activate RBPjκ in the viral context. This suggests a model whereby KSHV alters ICN-RBPjκ gene regulation. When the architecture of this pair of head-to-head RBPjκ binding sites is changed, the sites now respond exclusively to the viral transactivator RTA and no longer to the host mediator ICN.

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