Downregulation of p56(lck) tyrosine kinase activity in T cells of squirrelmonkeys (Saimiri sciureus) correlates with the nontransforming and apathogenic properties of herpesvirus saimiri in its natural host

Herpesvirus saimiri is capable of transforming T lymphocytes of various pri mate species to stable growth in culture. The interaction of the T-cellular tyrosine kinase p56(lck) with the transformation-associated viral protein Tip has been shown before to activate the kinase and provides one model for the T-cell-specific transformation by herpesvirus saimiri subgroup C strai ns. In contrast to other primate species, squirrel monkeys (Saimiri sciureu s) are naturally infected with the virus without signs of lymphoma or other disease. Although the endogenous virus was regularly recovered from periph eral blood cells from squirrel monkeys, we observed that the T cells lost t he virus genomes in culture. Superinfection with virus strain C488 did not induce growth transformation, in contrast to parallel experiments with T ce lls of other primate species. Surprisingly, p56(lck) was enzymatically inac tive in primary T-cell lines derived from different squirrel monkeys, altho ugh the T cells reacted appropriately to stimulatory signals. The cDNA sequ ence revealed minor point mutations only, and transfections in COS-7 cells demonstrated that the S. sciureus lck gene codes for a functional enzyme. I n S. sciureus, the tyrosine kinase p56(lck) was not activated after T-cell stimulation and enzymatic activity could not be induced by Tip of herpesvir us saimiri C488. However, the suppression of p56(lck) was partially release d after administration of the phosphatase inhibitor pervanadate. This argue s for unique species-specific conditions in T cells of S. sciureus which ma y interfere with the transforming activity and pathogenicity of herpesvirus saimiri subgroup C strains in their natural host.