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Human JC virus cAMP response elements functional for enhanced glial cell expression in differentiating embryonal
K U Kumar1, D L Reddy, M M Pater
1Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Virology
|January 15, 1996
Summary
JC virus (JCV) expression in glial cells is specifically enhanced by cyclic AMP (cAMP). This response is mediated by the JCV cAMP response element (CRE) and involves a 43-kDa glial cell protein.
Area of Science:
- Neurovirology
- Molecular Biology
- Cellular Biology
Background:
- Human JC virus (JCV) exhibits glial cell-specific growth and expression, implicated in brain lesions, particularly in AIDS patients.
- The regulatory region of JCV contains two 98-bp tandem repeats with sequences homologous to the cAMP response element (CRE).
Purpose of the Study:
- To investigate the role of the JCV repeat region's TGAGCTCA sequences (CRE) in glial cell-specific expression.
- To determine the effect of cAMP on the JCV early promoter (JCVE) in glial cells.
Main Methods:
- Site-directed mutagenesis to assess the in vivo role of the JCV CRE.
- In vivo and in vitro transcription assays using glial and P19 embryonal carcinoma cells.
- Mobility shift assays, Southwestern blot, and UV crosslinking to identify protein interactions with the CRE.
Main Results:
- JCVE expression increased threefold in response to cAMP specifically in glial cells, where JCV is efficiently expressed.
- Mutagenesis confirmed the in vivo role of the JCV CRE in mediating this cAMP response.
- A 43-kDa glial cell protein was identified that interacts with the JCV CRE in a cAMP-dependent manner.
Conclusions:
- JCVE expression is specifically upregulated by cAMP in glial cells via the JCV CRE.
- A specific glial cell protein interaction with the JCV CRE is crucial for this cAMP-mediated regulation.