| Herpesvirus saimiri (Saimirine herpesviridae -2; HVS) causes lethal T-lymphoproliferative diseases in the susceptible species and transforms T lymphocytes, including human ones, to continuous growth in vitro. HVS-induced transformation of T cells is becoming an important experimental tool for immortalization of antigen-specific T-cell clones, minor populations of T lymphocytes, and growth-defective T cells, as well as for the studies of HIV replication in T cells. Two proteins of HVS subgroup C, Tip and StpC, have been shown to be essential for T-cell transformation by this virus. In spite of the important role of these proteins, their biological functions and molecular mechanisms of their action remain insufficiently understood. In order to answer the question if Tip and/or StpC are sufficient for transformation and to elucidate further the effects of StpC and/or Tip on T cells, we transduced peripheral blood T lymphocytes, using an efficient lentiviral gene transfer system, to express Tip and/or StpC in the absence of other HVS proteins. Our results indicate that Tip exerts a specific inhibitory effect on IL-2 production by human T lymphocytes. Furthermore, Tip exhibits a considerable apoptosis-inducing activity both in primary and lymphoblastoid T cells, which appears to be the reason for the observed decrease in IL-2 production. Our study demonstrates that the apoptotic effect of Tip in T cells is mediated by Fas and requires the presence of active Lck in the cell. The presence of StpC could not inhibit the apoptotic role of Tip. Hence, expression of Tip and StpC, independent of other HVS proteins were not sufficient to transform T cells. |
