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Journal article
JCPyV T-Antigen Activation of the Anti-Apoptotic Survivin Promoter-Its Role in the Development of Progressive Multifocal Leukoencephalopathy
Viruses, v 12(11), p1253
03 Nov 2020
PMID: 33153187
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the CNS, resulting from the lytic infection of oligodendrocytes by the human neurotropic polyomavirus JC (JCPyV), typically associated with severe immunocompromised states and, in recent years, with the use of immunotherapies. Apoptosis is a homeostatic mechanism to dispose of senescent or damaged cells, including virally infected cells, triggered in the vast majority of viral infections of the brain. Previously, we showed upregulation of the normally dormant anti-apoptotic protein Survivin in cases of PML, which-in vitro-resulted in protection from apoptosis in JCPyV-infected primary cultures of astrocytes and oligodendrocytes. In the present study, we first demonstrate the absence of apoptotic DNA fragmentation and the lack of caspase activity in 16 cases of PML. We also identified the viral protein large T-Antigen as being responsible for the activation of the Survivin promoter. Chromatin Immunoprecipitation assay shows a direct binding between T-Antigen and the Survivin promoter DNA. Finally, we have identified the specific region of T-Antigen, spanning from amino acids 266 and 688, which binds to Survivin and translocates it to the nucleus, providing evidence of a mechanism that results in the efficient replication of JCPyV and a potential target for novel therapies.
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Details
- Title
- JCPyV T-Antigen Activation of the Anti-Apoptotic Survivin Promoter-Its Role in the Development of Progressive Multifocal Leukoencephalopathy
- Creators
- Luis Del Valle - Neurological Cancer Research, Stanley S. Scott Cancer Center, Departments of Medicine and Pathology, Louisiana State University Health, New Orleans, LA 70112, USA.Thersa Sweet - Drexel UniversityAmanda Parker-Struckhoff - Neurological Cancer Research, Stanley S. Scott Cancer Center, Louisiana State University Health, New Orleans, LA 70112, USA.Georgina Perez-Liz - Drexel UniversitySergio Piña-Oviedo - University of Arkansas for Medical Sciences
- Publication Details
- Viruses, v 12(11), p1253
- Publisher
- MDPI
- Grant note
- R01 NS055644 / NINDS NIH HHS P30 GM114732 / NIGMS NIH HHS P20 GM21288 / NIGMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics; A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000594281600001
- Scopus ID
- 2-s2.0-85095783050
- Other Identifier
- 991019167590004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Virology