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J Virol, July 1998, p. 6155-6158, Vol. 72, No. 7
Department of Microbiology and
Immunology1 and
Cancer
Center,3 University of Rochester Medical
Center, Rochester, New York 14642, and
Yerkes Regional
Primate Research Center and Emory University, Atlanta, Georgia
303222
Received 29 December 1997/Accepted 30 March 1998
The PBj14 isolate of the simian immunodeficiency virus SIVsmmPBj14
is unique among primate lentiviruses in its ability to induce
lymphocyte proliferation and acutely lethal disease. The studies
reported here show that viral induction of T-cell proliferation requires accessory cells, such as primary monocytes or Raji B-lymphoma cells, as well as the presence of a putative immunoreceptor
tyrosine-based activation motif within the viral Nef protein.
Addition of CTLA4-immunoglobulin fusion protein or anti-B7 antibodies
to virally infected T cells led to substantial, but not complete,
inhibition of monocyte-costimulated T-cell proliferation
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Costimulatory Pathways in Lymphocyte Proliferation
Induced by the Simian Immunodeficiency Virus SIVsmmPBj14
and
suggesting
that both CD28/B7-dependent and non-CD28-dependent pathways may
contribute to the costimulation of virally induced lymphoproliferation.
Finally, cyclosporin A, a specific inhibitor of the
calcium-calmodulin-regulated phosphatase activity of
calcineurin, which influences activation of the transcription factor
nuclear factor of activated T cells, was shown to block virally
mediated T-cell proliferation. Taken together, these findings suggest
that the effect of SIVsmmPBj14 on T-cell activation may be functionally
analogous, at least in part, to the effect of engagement of the T-cell
receptor.
*
Corresponding author. Mailing address: Department
of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642. Phone: (716) 275-3216. Fax: (716) 473-2361. E-mail: DWRT{at}BPHVAX.BIOPHYSICS.ROCHESTER.EDU.
Present address: Division of Molecular Medicine, Fred Hutchinson
Cancer Research Center, Seattle, WA 98105.
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