JC virus (JCV) is a human polyoma virus that has been associated with neurooncogenesis in several animal species. JCV can induce neural tumors in mice and hamsters as well as in nonhuman primates, e.g., owl and squirrel monkeys. In this project, we will utilize this oncogenic effect to study the immunobiology of CNS-derived tumors. There is evidence to suggest that brain tumors induce immunoregulatory abnormalities within their hosts. We plan to utilize the oncogenic potential of the human neurotropic virus (JCV) early protein, T-antigen, as a tool for inducing CNS-origin tumors. These tissues will be analyzed for their ability to induce a blood-brain barrier. The ability of these tumors to serve as immune targets will be assessed by comparing their ability to be rejected using xeno, allo, and homografts. Their immunogenicity will also be assessed by determining whether they are targeted by encephalitogenic lymphocytes, as we have demonstrated for normal astrocytes. Studies will be performed to evaluate the role of cytokines, including transforming growth factor (TGFbeta), on expression and activity of genes involved in the control of cell and tumor growth including tumor suppresses pRb, p107, and pRb2/p130, and the E2F family of key regulatory proteins in CNS tumors. Through this collaborative research we will be able to address several key questions related to the immunobiology, malignant transformation, and the cell cycle regulatory pathways of tumor cells in the CNS.
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