The Polyomavirus JC (JCV) causes the demyelinating disease progressive multifocal leukoencephalopathy (PML). Infection by JCV is very common in childhood after which the virus enters a latent state, the mechanisms of which are poorly understood. Under conditions of severe immunosuppression, especially acquired immunodeficiency syndrome (AIDS), JCV may reactivate to cause PML. JC viral proteins expression is regulated by the JCV non-coding control region (NCCR), which contains binding sites for cellular transcriptional factors which regulate JCV transcription. Our earlier studies indicate that reactivation occurs within glial cells due to the action of cytokines such as TNF-⍺, which stimulate viral gene expression. In this study, we have examined the role of cytokines interferon-⍺ or -β which, in contrast, have a negative effect on JCV transcriptional regulation. Treatment of glial cells with interferon-⍺ or -β increased the endogenous level of C/EBPβ-LIP in a time-dependent manner. Furthermore, the negative regulatory role of interferon-⍺ or -β in JCV early and late transcription and viral replication was more pronounced in the presence of C/EBPβ-LIP. Knock-down of C/EBPβ-LIP (liver inhibitory protein) by shRNA targeting C/EBPβ-LIP reversed the inhibitory effect on JCV viral replication. Therefore, these data suggest that interferon-⍺ or -β negatively regulates JCV through induction of C/EBPβ-LIP, which together with other cellular transcriptional factors may control the balance between JCV latency and activation leading to PML. This balance may be regulated by proinflammatory cytokines in the brain, such as IFN-?. / Biomedical Neuroscience
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/6582 |
| Date | January 2021 |
| Creators | May, Dana, 0000-0003-2456-9456 |
| Contributors | Wollebo, Hassen S., Burdo, Tricia H., Wollebo, Hassen S., Burdo, Tricia H., Kaminski, Rafal |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 92 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/6564, Theses and Dissertations |
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