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Journal of Virology, May 1999, p. 3913-3919, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role of Cellular Tumor Necrosis Factor Receptor-Associated Factors in NF-kappa B Activation and Lymphocyte Transformation by Herpesvirus Saimiri STP

Heuiran Lee,1,3 Joong-Kook Choi,1 Mengtao Li,1 Ken Kaye,2 Elliott Kieff,2 and Jae U. Jung1,*

Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-91021; Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 021152; and Yonsei Cancer Center, Institute of Cancer Research, Yonsei University College of Medicine, 134 Sinchon-Dong, Seoul, Korea3

Received 1 December 1998/Accepted 15 February 1999

The STP oncoproteins of the herpesvirus saimiri (HVS) subgroup A strain 11 and subgroup C strain 488 are now found to be stably associated with tumor necrosis factor receptor-associated factor (TRAF) 1, 2, or 3. Mutational analyses identified residues of PXQXT/S in STP-A11 as critical for TRAF association. In addition, a somewhat divergent region of STP-C488 is critical for TRAF association. Mutational analysis also revealed that STP-C488 induced NF-kappa B activation that was correlated with its ability to associate with TRAFs. The HVS STP-C488 P10right-arrowR mutant was deficient in human T-lymphocyte transformation to interleukin-2-independent growth but showed wild-type phenotype for marmoset T-lymphocyte transformation in vitro and in vivo. The STP-C488 P10right-arrowR mutant was also defective in Rat-1 fibroblast transformation, and fibroblast cell transformation was blocked by a TRAF2 dominant-negative mutant. These data implicate TRAFs in STP-C488-mediated transformation of human lymphocytes and rodent fibroblasts. Other factors are implicated in immortalization of common marmoset T lymphocytes and may also be critical in the transformation of human lymphocytes and rodent fibroblasts.

* Corresponding author. Mailing address: New England Regional Primate Research Center, Harvard Medical School, 1 Pine Hill Dr., P.O. Box 9102, Southborough, MA 01772. Phone: (508) 624-8083. Fax: (508) 624-8190. E-mail: jae_jung{at}hms.harvard.edu.

Journal of Virology, May 1999, p. 3913-3919, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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