|
|
Blood, 15 May 2005, Vol. 105, No. 10, pp. 4028-4034.
Prepublished online as a Blood First Edition Paper on February 1, 2005; DOI 10.1182/blood-2004-09-3569.
 Previous Article | Next Article 
Submitted September 14, 2004
Accepted January 12, 2005
The targeting of primary effusion lymphoma cells for apoptosis by inducing lytic replication of human herpesvirus 8 while blocking virus production
Carmen M Klass, Laurie T Krug, Veronika P Pozharskaya, and Margaret K Offermann*
Winship Cancer Institute, Emory University, Atlanta, GA, USA
* Corresponding author; email: mofferm{at}emory.edu.
Primary Effusion Lymphoma (PEL) is a B-cell lymphoma in which human herpesvirus-8 (HHV-8) is found within all tumor cells and represents a target for selectively destroying tumor cells. HHV-8 is latent in most PEL cells and hence resistant to antiviral agents that inhibit lytic replication. We demonstrate that PEL cell lines containing HHV-8 without and with co-infection with Epstein-Barr virus responded to the antiseizure medication valproate with entry into the lytic cascade and production of infectious virus. Minimal cell death occurred when non-infected BL-41 cells were incubated with valproate, whereas apoptosis occurred in response to valproate in PELs that supported lytic replication of HHV-8. The antiviral agents ganciclovir and phosphonoformic acid (PFA) blocked valproate-induced production of infectious virus without blocking entry into the lytic cascade, and apoptosis occurred at levels that were as high as when virus production was not blocked. Ganciclovir and PFA also prevented most valproate-induced expression of the late lytic viral transcript ORF-26, they but they did not block the induction of either vIL-6 or vGPCR. These studies provide evidence that incubation of PELs with valproate in the presence of ganciclovir or PFA can selectively target tumor cells for apoptosis without increasing viral load.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
V. Majerciak, K. Yamanegi, E. Allemand, M. Kruhlak, A. R. Krainer, and Z.-M. Zheng
Kaposi's Sarcoma-Associated Herpesvirus ORF57 Functions as a Viral Splicing Factor and Promotes Expression of Intron-Containing Viral Lytic Genes in Spliceosome-Mediated RNA Splicing
J. Virol.,
March 15, 2008;
82(6):
2792 - 2801.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-B. Chen, A. Rahemtullah, and E. Hochberg
Primary Effusion Lymphoma
Oncologist,
May 1, 2007;
12(5):
569 - 576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Majerciak, N. Pripuzova, J. P. McCoy, S.-J. Gao, and Z.-M. Zheng
Targeted Disruption of Kaposi's Sarcoma-Associated Herpesvirus ORF57 in the Viral Genome Is Detrimental for the Expression of ORF59, K8{alpha}, and K8.1 and the Production of Infectious Virus
J. Virol.,
February 1, 2007;
81(3):
1062 - 1071.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Majerciak, K. Yamanegi, and Z.-M. Zheng
Gene Structure and Expression of Kaposi's Sarcoma-Associated Herpesvirus ORF56, ORF57, ORF58, and ORF59
J. Virol.,
December 15, 2006;
80(24):
11968 - 11981.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-h. Feng and S. C. Kenney
Valproic Acid Enhances the Efficacy of Chemotherapy in EBV-Positive Tumors by Increasing Lytic Viral Gene Expression.
Cancer Res.,
September 1, 2006;
66(17):
8762 - 8769.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
