This is a proposal to establish a Neuropathology and Tissue Culture Core which will help the overall program to determine the pathological effects of HIV-1 and JCV in the brain and to elucidate the molecular pathways through which theses viruses interact. We will provide surgical and autopsy brain tissue samples from AIDS and non-AIDS PML patients diagnosed with HIV-1 encephalopathy, to be used primarily in Projects 1, 2 and 3, for the co-localization of HIV-1 or JCV proteins with cellular proteins relevant to viral activities. We will perform, in conjunction with Project 1, pathological analyses of tissue samples from mice transgenically expressing JCV T-antigen under the control of the JCV early promoter. We will provide highly purified cultures of microglial, oligodendrocytes and astrocytes from human fetal CNS tissue, and from human adult CNS tissue. As a service to all three projects, we will maintain cultures of established permanent cell lines, including the progenitor CG-4 cells, which will be utilized in Projects 1 and 2. Finally, we will provide quality control of primary cultures and cell lines, and evaluate the differentiation state of CG-4 cells by immunocytochemical staining with cell type- specific markers. The proposed services will help provide essential material for the three participant projects, aimed at deciphering the role of host regulatory proteins in interacting with HIV-1 and JCV viral factors in the pathogenesis off two important CNS disorders.
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