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J Virol, April 1998, p. 3138-3145, Vol. 72, No. 4
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-
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
. 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.
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