Related Experiment Videos
JC virus-induced changes in cellular gene expression in primary human astrocytes
Sujatha Radhakrishnan1, Jessica Otte, Sahnila Enam
1Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
Journal of Virology
|September 13, 2003
Summary
JC virus (JCV) infection in human astrocytes alters gene expression, boosting cell proliferation and inflammatory genes. These changes, including increased cyclin proteins, are observed in brain tissue from progressive multifocal leukoencephalopathy (PML) patients.
Area of Science:
- Neurovirology
- Molecular Biology
- Cellular Biology
Background:
- JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease, particularly in immunocompromised individuals.
- JCV replication in glial cells is initiated by cell-type-specific promoter transcription, leading to severe neurological complications.
Purpose of the Study:
- To compare the transcriptional profile of cellular genes in human astrocytes following JCV infection.
- To investigate the role of altered gene expression in JCV-induced pathogenesis.
Main Methods:
- Primary cultures of human astrocytes were infected with JCV.
- Oligonucleotide-based microarray analysis was used to assess the transcriptional profile of approximately 12,600 genes.
- Western blot analysis and immunohistochemistry were employed to validate gene expression changes at the protein level.
Main Results:
- JCV infection significantly altered the transcription of cellular genes, with 355 genes enhanced and 130 genes decreased.
- Upregulated genes were associated with cell proliferation (e.g., cyclin A, cyclin B1), signaling pathways (e.g., TGF-β receptor 1), and inflammatory responses (e.g., cyclo-oxygenase-2).
- Protein levels of upregulated genes increased during the infection, and cell cycle proteins (cyclins A, B1, E, Cdk2) were detected in astrocytes within PML brain lesions.
Conclusions:
- Microarray analysis is a valuable tool for predicting gene expression changes in JCV-infected cells.
- JCV infection induces significant alterations in host cell gene expression, promoting cell proliferation and inflammation.
- The observed changes in gene and protein expression are relevant to the pathogenesis of PML in neuro-AIDS patients.