To understand the principal molecular mechanisms and biochemical pathways involved and activated in tumors of T-cell origin we have chosen to study Herpesvirus saimiri. This virus causes exclusively T-cell lymphomas or T-cell leukemias in many New World monkey species. This model offers several advantages over other primate tumorviruses; i./ experimental animal systems are available, ii./ lymphomas are induced very rapidly, iii./ in vitro immortalization assay is available, and iv./ the virus can be grown productively to high titers. The biology of H.
s aimi ri is unique among primate tumorviruses since it transforms either cytotoxic T-cells or NK cells. Also, the mechanism of oncogenic transformation by H.
s aimi ri is unique among DNA tumorviruses. We have identified a region of the viral genome required for oncogenicity, but non-essential for viral multiplication. Surprisingly, the DNA sequence of this region is extremely variable among different groups of viruses, and this variability is also reflected in different oncogenic properties. Our preliminary data suggest that H.
s aimi ri tumor cells secrete growth factor(s) and exhibit properties consistent with autocrine secretion. We have also demonstrated that these T-cells express the receptor for the T-cell growth factor IL-2. The studies proposed here will concentrate on molecular and biochemical characterization of growth factors and specific receptors in our system by exploiting the advantages of the in vitro immortalization assay that has recently become available. The final goal is to understand relationships between malignant transformation and growth factors, and identify viral genes that are involved in the activation of growth factors and receptors.
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