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Title: IFN-α and β restrict JC virus replication in primary human fetal glial cells : implications for progressive multifocal leukoencephalopathy therapy
IFN-alpha and beta restrict JC virus replication in primary human fetal glial cells
Authors: Co, Juliene Kimberly G.
Keywords: Interferon -- Therapeutic use
Antiviral agents
Issue Date: 2006
Abstract: Among the severely immunocompromised, IC virus ( JCV) may cause a fatal demyelinating disease, progressive multifoca1leukoencephalopathy (PML). Highly active antiretroviral therapy (HAART) is the standard treatment for PML patients, but it is effective in only 50% of PML patients. We previously demonstrated induction of genes associated with interferon (IFN) antiviral response pathway in primary human fetal glial (PHFG) cells, specifically at later stages of JCV replication (Virology 2006; 345:457). The objective of this study was to analyze specific viral events required to induce interferon-stimulated genes (ISG), and to assess the potential antiviral effects of IFN-α and -β on JCV replication. PHFG cells were infected with 50 HAU of JCV (Madl) or UV-inactivated JCV and grown in the presence of 100 U/mL of IFN- α. or-β. Quantitation of JCV DNA, mRNA transcripts, and T antigen (TAg) expression were measured at days 3,5,8, and 15 post-infection using quantitative- rea1-time-PCR, -RT-PCR, and Western blotting techniques. Our data indicate that JCV induces ISG in PHFG cells, and demonstrates direct antiviral effect of IFN- α and -β on JCV replication. Previous studies have employed IFN as immunomodulators. Our study warrants further clinical trials to treat PML patients using IFN as an adjunct therapy, specifically focused on intrathecal route of administration.
Description: Thesis (M.S.)--University of Hawaii at Manoa, 2006.
Includes bibliographical references (leaves 62-69).
viii, 69 leaves, bound ill. 29 cm
URI/DOI: http://hdl.handle.net/10125/20442
Rights: All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
Appears in Collections:M.S. - Biomedical Sciences (Tropical Medicine)



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