Journal article
Effects of JC Virus Infection on Anti-Apoptotic Protein Survivin in Progressive Multifocal Leukoencephalopathy
The American journal of pathology, v 170(4), pp 1291-1304
01 Apr 2007
PMID: 17392168
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system resulting from the productive infection of oligodendrocytes by the opportunistic polyomavirus JC virus (JCV). Apoptosis is a host defense mechanism to dispose of damaged cells; however, certain viruses have the ability to deregulate apoptotic pathways to complete their life cycles. One such pathway involves survivin, a member of the inhibitor of apoptosis family, which is abundantly expressed during development in proliferating tissues but should be absent in normal, terminally differentiated cells. Immunohistochemistry performed in 20 cases of PML revealed the presence of survivin in JCV-infected oligodendrocytes and bizarre astrocytes within demyelinated plaques. Survivin up-regulation was also found in oligodendroglial and astrocytic cultures infected with JCV. Cell cycle analysis and DNA laddering demonstrated a significantly lower number of cells undergoing apoptosis on JCV infection compared with noninfected cultures; small interfering RNA inhibition of survivin resulted in a dramatic increase in apoptotic cells in JCV-infected cultures. This is the first report describing the activation of survivin by JCV infection
in vitro
and in PML clinical cases. These observations provide new insights into the anti-apoptotic mechanisms used by JCV to complete its lytic cycle and may suggest new therapeutic targets for PML.
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Details
- Title
- Effects of JC Virus Infection on Anti-Apoptotic Protein Survivin in Progressive Multifocal Leukoencephalopathy
- Creators
- Sergio Piña-Oviedo - Temple UniversityKatarzyna Urbanska - Temple UniversitySujatha Radhakrishnan - Temple UniversityThersa Sweet - Temple UniversityKrzysztof Reiss - Temple UniversityKamel Khalili - Temple UniversityLuis Del Valle - Temple University
- Publication Details
- The American journal of pathology, v 170(4), pp 1291-1304
- Publisher
- Elsevier
- Grant note
- R01 NS41209-01 / National Institute of Neurological Disorders and Stroke R01 NS055644-01 / National Institutes of Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000245233000016
- Scopus ID
- 2-s2.0-34247897171
- Other Identifier
- 991021448057604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pathology