Related Experiment Videos
T' proteins influence JC virus biology
Richard J Frisque1, Brigitte Bollag, Shiva K Tyagarajan
1Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. RJF6@psu.edu
Journal of Neurovirology
|April 24, 2003
Summary
JC virus early mRNA splicing produces multiple proteins. New research identifies an exonic splicing enhancer and reveals T
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- JC virus (JCV) is a human polyomavirus with a complex early mRNA splicing.
- Alternative splicing of JCV early mRNA generates five distinct transcripts encoding various T-antigens.
- Differential regulation of splicing occurs in transformed versus lytically infected cells and over time during infection.
Purpose of the Study:
- To investigate the role of exonic splicing enhancers in JCV mRNA splicing.
- To elucidate the functions of the T' proteins, which are newly identified JCV early proteins.
- To analyze the in vivo interactions of viral proteins with cellular tumor suppressor proteins.
Main Methods:
- Site-directed mutagenesis was used to identify a potential exonic splicing enhancer.
- Genetic and biochemical approaches were employed to study T' protein functions.
- G418 selection was utilized to create cell lines expressing individual JCV early proteins.
Main Results:
- Mutation of a potential exonic splicing enhancer altered splice site usage in JCV early mRNA.
- T' proteins were found to enhance viral DNA replication and bind differentially to pRB family proteins in vitro.
- Cell lines expressing individual T antigens or T' proteins revealed that T antigen may induce apoptosis, potentially inhibited by other JCV early proteins.
- In vivo analysis showed differential binding of viral proteins to pRB family members compared to in vitro findings.
Conclusions:
- An exonic splicing enhancer plays a role in regulating JCV early mRNA splicing.
- T' proteins are involved in viral DNA replication and modulate interactions with cellular tumor suppressors.
- JCV T antigen may induce apoptosis, with potential modulation by other JCV early proteins, highlighting complex viral-host interactions.