This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kraft, M. S.
Right arrow Articles by Meinl, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kraft, M. S.
Right arrow Articles by Meinl, E.

 Previous Article  |  Next Article 

J Virol, April 1998, p. 3138-3145, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Herpesvirus Saimiri Transforms Human T-Cell Clones to Stable Growth without Inducing Resistance to Apoptosis

Michael S. Kraft,1 Golo Henning,1 Helmut Fickenscher,1 Doris Lengenfelder,1 Jürg Tschopp,2 Bernhard Fleckenstein,1 and Edgar Meinl1,*

Institut für Klinische und Molekulare Virologie, University of Erlangen-Nürnberg, D-91054 Erlangen, Germany,1 and Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland2

Received 6 November 1997/Accepted 19 December 1997

Herpesvirus saimiri (HVS) transforms human T cells to stable growth in vitro. Since HVS codes for two different antiapoptotic proteins, growth transformation by HVS might be expected to confer resistance to apoptosis. We found that the expression of both viral antiapoptotic genes was restricted to cultures with viral replication and absent in growth-transformed human T cells. A comparative examination of HVS-transformed T-cell clones and their native parental clones revealed that the expression of Bcl-2, Bcl-XL, Bax, and members of the tumor necrosis factor receptor (TNF-R) superfamily with a death domain, namely, TNF-RI, CD95, and TRAMP, were not modulated by HVS. Expression of CD30 was induced in HVS-transformed T cells, and these cells also expressed the CD30 ligand. Uninfected and transformed T cells were sensitive to CD95 ligation but resistant to apoptosis mediated by TRAIL or soluble TNF-alpha . CD95 ligand was constitutively expressed on transformed but not uninfected parental T cells. Both cell types showed similar sensitivity to cell death induction or inhibition of T-cell activation mediated by irradiation, oxygen radicals, dexamethasone, cyclosporine, and prostaglandin E2. Altogether, this study strongly suggests that growth transformation by HVS is based not on resistance to apoptosis but, rather, on utilization of normal cellular activation pathways.


* Corresponding author. Mailing address: Institut für Klinische und Molekulare Virologie, Schlossgarten 4, D-91054 Erlangen, Germany. Phone: 49-9131-853786. Fax: 49-9131-856493. E-mail: ermeinl{at}viro.med.uni-erlangen.de.




This article has been cited by other articles:

  • Martin-Fernandez, J. M., Cabanillas, J. A., Rivero-Carmena, M., Lacasa, E., Pardo, J., Anel, A., Ramirez-Duque, P. R., Merino, F., Rodriguez-Gallego, C., Regueiro, J. R. (2005). Herpesvirus saimiri-transformed CD8+ T cells as a tool to study Chediak-Higashi syndrome cytolytic lymphocytes. J. Leukoc. Biol. 77: 661-668 [Abstract] [Full Text]  
  • Holm, G. H., Zhang, C., Gorry, P. R., Peden, K., Schols, D., De Clercq, E., Gabuzda, D. (2004). Apoptosis of Bystander T Cells Induced by Human Immunodeficiency Virus Type 1 with Increased Envelope/Receptor Affinity and Coreceptor Binding Site Exposure. J. Virol. 78: 4541-4551 [Abstract] [Full Text]  
  • Verma, S. C., Robertson, E. S. (2003). ORF73 of Herpesvirus Saimiri Strain C488 Tethers the Viral Genome to Metaphase Chromosomes and Binds to cis-Acting DNA Sequences in the Terminal Repeats. J. Virol. 77: 12494-12506 [Abstract] [Full Text]  
  • Glykofrydes, D., Niphuis, H., Kuhn, E. M., Rosenwirth, B., Heeney, J. L., Bruder, J., Niedobitek, G., Müller-Fleckenstein, I., Fleckenstein, B., Ensser, A. (2000). Herpesvirus Saimiri vFLIP Provides an Antiapoptotic Function but Is Not Essential for Viral Replication, Transformation, or Pathogenicity. J. Virol. 74: 11919-11927 [Abstract] [Full Text]  
  • Rivero-Carmena, M., Porras, O., Pelaez, B., Pacheco-Castro, A., Gatti, R. A., Regueiro, J. R. (2000). Membrane and transmembrane signaling in Herpesvirus saimiri-transformed human CD4+ and CD8+ T lymphocytes is ATM-independent.. Int Immunol 12: 927-935 [Abstract] [Full Text]  
  • Virgin, H. W. IV, Presti, R. M., Li, X.-Y., Liu, C., Speck, S. H. (1999). Three Distinct Regions of the Murine Gammaherpesvirus 68 Genome Are Transcriptionally Active in Latently Infected Mice. J. Virol. 73: 2321-2332 [Abstract] [Full Text]  
  • Derfuss, T., Fickenscher, H., Kraft, M. S., Henning, G., Lengenfelder, D., Fleckenstein, B., Meinl, E. (1998). Antiapoptotic Activity of the Herpesvirus Saimiri-Encoded Bcl-2 Homolog: Stabilization of Mitochondria and Inhibition of Caspase-3-Like Activity. J. Virol. 72: 5897-5904 [Abstract] [Full Text]