Role of cellular tumor necrosis factor receptor-associated factors in NF-kappa B activation and lymphocyte transformation by herpesvirus Saimiri STP

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 an alyses identified residues of PXQXT/S in STP-A11 as critical for TRAF assoc iation. In addition, a somewhat divergent region of STP-C488 is critical fo r TRAF association. Mutational analysis also revealed that STP-C488 induced NF-kappa B activation that was correlated with its ability to associate wi th TRAFs. The HVS STP-C488 P-10-->R mutant was deficient in human T-lymphoc yte transformation to interleukin-2-independent growth but showed wild-type phenotype for marmoset T-lymphocyte transformation in vitro and in vivo. T he STP-C488 P-10-->R mutant was also defective in Rat-1 fibroblast transfor mation, and fibroblast cell transformation was blocked by a TRAF2 dominant- negative mutant. These data implicate TRAFs in STP-C488-mediated transforma tion of human lymphocytes and rodent fibroblasts. Other factors are implica ted in immortalization of common marmoset T lymphocytes and may also be cri tical in the transformation of human lymphocytes and rodent fibroblasts.