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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS030916-11
Application #
6660984
Study Section
Special Emphasis Panel (ZNS1)
Project Start
2002-09-01
Project End
2003-08-31
Budget Start
Budget End
Support Year
11
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Temple University
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
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PiƱa-Oviedo, Sergio; Khalili, Kamel; Del Valle, Luis (2009) Hypoxia inducible factor-1 alpha activation of the JCV promoter: role in the pathogenesis of progressive multifocal leukoencephalopathy. Acta Neuropathol 118:235-47
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Kaminski, Rafal; Darbinyan, Armine; Merabova, Nana et al. (2008) Protective role of Puralpha to cisplatin. Cancer Biol Ther 7:1926-35
Perez-Liz, Georgina; Del Valle, Luis; Gentilella, Antonio et al. (2008) Detection of JC virus DNA fragments but not proteins in normal brain tissue. Ann Neurol 64:379-87

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