|
|
Blood, 1 January 2006, Vol. 107, No. 1, pp. 277-284.
Prepublished online as a Blood First Edition Paper on September 8, 2005; DOI 10.1182/blood-2005-06-2350.
 Previous Article | Next Article 
Submitted June 13, 2005
Accepted August 19, 2005
The KSHV G protein-coupled receptor inhibits lytic gene transcription in primary effusion lymphoma cells via p21-mediated inhibition of Cdk2
Mark L Cannon*, Ethel Cesarman, and Chris Boshoff
The Division of International Medicine and Infectious Diseases, Department of Medicine, Weill Medical College of Cornell University, New York, NY, USA; The Wolfson Institute for Biomedical Research, University College London, London, United Kingdom
The Department of Pathology, Weill Medical College of Cornell University, New York, NY, USA
The Wolfson Institute for Biomedical Research, University College London, London, United Kingdom
* Corresponding author; email: m.cannon{at}ucl.ac.uk.
Kaposi's sarcoma (KS), an endothelial cell tumor, is the most common AIDS-associated malignancy worldwide. KS-associated herpesvirus (KSHV) is an etiologic agent in all forms of KS and is also associated with primary effusion lymphoma (PEL) and multicentric Castleman's disease. KSHV encodes many proteins involved in cell proliferation and angiogenesis. One of these is the vGPCR, a constitutively active homologue of the human IL-8 receptor. vGPCR is considered a viral oncogene but we have found that its overexpression inhibits growth of PEL cells. In the current study we find that vGPCR causes a G0/G1 arrest via upregulation of p21cip. This effect is p53-independent and inhibits the S-phase cyclin-dependent kinase, Cdk2. Using a Cdk2-DN construct, we show that chemical induction of the KSHV lytic genes ORF50 and ORF26 is inhibited by vGPCR via its effect on Cdk2. We conclude therefore, that Cdk2 is likely required for the normal latent-lytic switch and that vGPCR can interfere with successful KSHV replication. We argue that overexpression of vGPCR, outside the context of lytic replication, could delay or prevent lytic phase-associated host cell death; this would explain how vGPCR, despite being a lytic transcript, could have important paracrine effects on surrounding KSHV-infected and uninfected cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
G. Sandford, Y. B. Choi, and J. Nicholas
Role of ORF74-Encoded Viral G Protein-Coupled Receptor in Human Herpesvirus 8 Lytic Replication
J. Virol.,
December 15, 2009;
83(24):
13009 - 13014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. T. Krug, C. M. Collins, L. M. Gargano, and S. H. Speck
NF-{kappa}B p50 Plays Distinct Roles in the Establishment and Control of Murine Gammaherpesvirus 68 Latency
J. Virol.,
May 15, 2009;
83(10):
4732 - 4748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Bu, D. Palmeri, R. Krishnan, R. Marin, V. M. Aris, P. Soteropoulos, and D. M. Lukac
Identification of Direct Transcriptional Targets of the Kaposi's Sarcoma-Associated Herpesvirus Rta Lytic Switch Protein by Conditional Nuclear Localization
J. Virol.,
November 1, 2008;
82(21):
10709 - 10723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. R. Rezaee, C. Cunningham, A. J. Davison, and D. J. Blackbourn
Kaposi's sarcoma-associated herpesvirus immune modulation: an overview
J. Gen. Virol.,
July 1, 2006;
87(7):
1781 - 1804.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
