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J Virol, May 1998, p. 3698-3704, Vol. 72, No. 5
Department of Microbiology and Molecular
Genetics1 and
Department of
Pathology,2 New England Regional Primate
Research Center, Harvard Medical School, Southborough, Massachusetts
01772-9102, and
Department of Applied Medical Sciences,
University of Southern Maine, Portland, Maine
04104-93003
Received 2 December 1997/Accepted 2 February 1998
STP-C488 (STP of herpesvirus saimiri [HVS] group C strain 488 [C488]) is the only virus-encoded protein found to associate with
cellular ras and activate ras signal
transduction pathways. To investigate an important role for
ras signal transduction in STP-dependent growth
transformation, we constructed recombinant strains of HVS C488 in which
the STP-C488 oncogene was replaced with cellular normal ras
(c-ras) or viral oncogenic ras (v-ras). Recombinant HVS
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Substitution of ras for the Herpesvirus
Saimiri STP Oncogene in Lymphocyte Transformation
STP/v-ras immortalized primary common
marmoset T lymphocytes to interleukin-2-independent growth as
efficiently as wild-type HVS C488 (wt HVS), while recombinant
HVS
STP/c-ras did so with low efficiency. Whereas wt HVS
immortalized CD4
CD8+ single-positive T
lymphocytes, HVS
STP/c-ras- and
HVS
STP/v-ras-immortalized cells were principally
CD4+ CD8+ double-positive T lymphocytes. In
addition, HVS
STP/v-ras-immortalized T cells showed a
high level of ras expression and exhibited an adherent
macrophage-like morphology. These phenotypes were likely caused by the
drastic activation of AP-1 transcriptional factor activity. Finally,
HVS
STP/v-ras and HVS
STP/c-ras each
induced lymphoma in one of two common marmosets, although onset of
disease was more rapid with the v-ras virus. These results
demonstrate that ras can substitute for the STP oncogene of
HVS C488 to allow immortalized growth of primary lymphoid cells and
that an activated form of ras does so more efficiently than
the normal cellular form of ras.
*
Corresponding author. Mailing address: New England
Regional Primate Research Center, Harvard Medical School, 1 Pine Hill
Dr., Southborough, MA 01772. Phone: (508) 624-8083. Fax: (508)
624-8190. E-mail: jjung{at}warren.harvard.med.edu.
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