|
|
Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2072.
Submitted July 11, 2002
Accepted October 9, 2002
The human herpes virus 8 encoded viral FLICE inhibitory protein protects against growth factor withdrawal-induced apoptosis via NF- B activation
Qinmiao Sun, Hittu Matta, and Preet M Chaudhary*
Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA
Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA
* Corresponding author; email: preet.chaudhary{at}utsouthwestern.edu.
The human herpes virus 8 (HHV8)-encoded viral FLICE inhibitory protein (vFLIP) is believed to protect cells against death receptors-mediated apoptosis. In the present study we demonstrate that expression of HHV8 vFLIP in a growth factor-dependent TF-1 leukemia cell line protects against growth factor withdrawal-induced apoptosis. Unlike vector expressing cells, those expressing HHV8 vFLIP maintain their mitochondrial membrane potential upon withdrawal from growth factor and also exhibit a block in the activation of caspases. The protective effect of HHV8 vFLIP is associated with its ability to activate the NF- B pathway and is missing in the vFLIP encoded by Equine Herpes Virus 2 which lacks this activity. Inhibition of the NF-B pathway by IB super-repressor, lactacystin, MG132, arsenic trioxide and phenylarsine oxide reverses the protection against growth factor withdrawal-induced apoptosis conferred by HHV8 vFLIP. HHV8 vFLIP upregulates the expression of Bcl-xL, an anti-apoptotic member of the Bcl2 family, which is a known target of the NF-B pathway. Collectively, the above results suggest that HHV8 vFLIP-induced NF-B activation may contribute to cellular transformation seen in association with HHV8 infection by preventing the apoptosis of cells destined to die due to growth factor deprivation.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
V. Punj, H. Matta, S. Schamus, T. Yang, Y. Chang, and P. M. Chaudhary
Induction of CCL20 production by Kaposi sarcoma-associated herpesvirus: role of viral FLICE inhibitory protein K13-induced NF-{kappa}B activation
Blood,
May 28, 2009;
113(22):
5660 - 5668.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Konrad, E. Wies, M. Thurau, G. Marquardt, E. Naschberger, S. Hentschel, R. Jochmann, T. F. Schulz, H. Erfle, B. Brors, et al.
A Systems Biology Approach To Identify the Combination Effects of Human Herpesvirus 8 Genes on NF-{kappa}B Activation
J. Virol.,
March 15, 2009;
83(6):
2563 - 2574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Rowe, L. Lopes, N. Brown, S. Efklidou, T. Smallie, S. Karrar, P. M. Kaye, and M. K. Collins
Expression of vFLIP in a Lentiviral Vaccine Vector Activates NF-{kappa}B, Matures Dendritic Cells, and Increases CD8+ T-Cell Responses
J. Virol.,
February 15, 2009;
83(4):
1555 - 1562.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Thurau, G. Marquardt, N. Gonin-Laurent, K. Weinlander, E. Naschberger, R. Jochmann, K. R. Alkharsah, T. F. Schulz, M. Thome, F. Neipel, et al.
Viral Inhibitor of Apoptosis vFLIP/K13 Protects Endothelial Cells against Superoxide-Induced Cell Death
J. Virol.,
January 15, 2009;
83(2):
598 - 611.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F.-C. Ye, F.-C. Zhou, J.-P. Xie, T. Kang, W. Greene, K. Kuhne, X.-F. Lei, Q.-H. Li, and S.-J. Gao
Kaposi's Sarcoma-Associated Herpesvirus Latent Gene vFLIP Inhibits Viral Lytic Replication through NF-{kappa}B-Mediated Suppression of the AP-1 Pathway: a Novel Mechanism of Virus Control of Latency
J. Virol.,
May 1, 2008;
82(9):
4235 - 4249.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Xu and D. Ganem
Induction of chemokine production by latent Kaposi's sarcoma-associated herpesvirus infection of endothelial cells
J. Gen. Virol.,
January 1, 2007;
88(1):
46 - 50.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Grossmann, S. Podgrabinska, M. Skobe, and D. Ganem
Activation of NF-{kappa}B by the Latent vFLIP Gene of Kaposi's Sarcoma-Associated Herpesvirus Is Required for the Spindle Shape of Virus-Infected Endothelial Cells and Contributes to Their Proinflammatory Phenotype
J. Virol.,
July 15, 2006;
80(14):
7179 - 7185.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Pearce, S. Matsumura, and A. C. Wilson
Transcripts Encoding K12, v-FLIP, v-Cyclin, and the MicroRNA Cluster of Kaposi's Sarcoma-Associated Herpesvirus Originate from a Common Promoter
J. Virol.,
November 15, 2005;
79(22):
14457 - 14464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Rodriguez, N. Martinez, F. I. Camacho, E. Ruiz-Ballesteros, P. Algara, J.-F. Garcia, J. Menarguez, T. Alvaro, M. F. Fresno, F. Solano, et al.
Variability in the Degree of Expression of Phosphorylated I{kappa}B{alpha} in Chronic Lymphocytic Leukemia Cases With Nodal Involvement
Clin. Cancer Res.,
October 15, 2004;
10(20):
6796 - 6806.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. T. Krug, V. P. Pozharskaya, Y. Yu, N. Inoue, and M. K. Offermann
Inhibition of Infection and Replication of Human Herpesvirus 8 in Microvascular Endothelial Cells by Alpha Interferon and Phosphonoformic Acid
J. Virol.,
August 1, 2004;
78(15):
8359 - 8371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Matta and P. M. Chaudhary
Activation of alternative NF-{kappa}B pathway by human herpes virus 8-encoded Fas-associated death domain-like IL-1{beta}-converting enzyme inhibitory protein (vFLIP)
PNAS,
June 22, 2004;
101(25):
9399 - 9404.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Sun, S. Zachariah, and P. M. Chaudhary
The Human Herpes Virus 8-Encoded Viral FLICE-inhibitory Protein Induces Cellular Transformation via NF-{kappa}B Activation
J. Biol. Chem.,
December 26, 2003;
278(52):
52437 - 52445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Field, W. Low, M. Daniels, S. Howell, L. Daviet, C. Boshoff, and M. Collins
KSHV vFLIP binds to IKK-{gamma} to activate IKK
J. Cell Sci.,
September 15, 2003;
116(18):
3721 - 3728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
