Tip, an Lck-interacting protein of Herpesvirus saimiri, causes Fas- and Lck-dependent apoptosis of T lymphocytes.
Saimiriine herpesvirus-2 (Herpesvirus saimiri) transforms T lymphocytes, including human, to continuous growth in vitro. H. saimiri-induced transformation is becoming an important tool of T-cell biology, including studies of HIV replication. Two proteins of H. saimiri subgroup C, Tip and StpC, are essential for T-cell transformation. In spite of the important role of these proteins, their biological functions and the molecular mechanisms of their action remain insufficiently understood. To further elucidate the effects of Tip on T cells, we transduced T lymphocytes, using an efficient lentiviral gene transfer system, to express Tip in the absence of other H. saimiri proteins. Our results indicate that Tip specifically inhibits IL-2 production by human T lymphocytes. Furthermore, Tip promotes T-cell apoptosis, which appears to be the reason for the observed decrease in IL-2 production. Finally, the apoptotic effect of Tip in T cells is mediated by Fas and requires the presence of active Lck in the cell.
Hasham
Muneer G
MG
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Tsygankov
Alexander Y
AY
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002472:Cell Transformation, Viral; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D010750:Phosphoproteins; D014764:Viral Proteins; D019014:fas Receptor; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)