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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
PubMed

Insights

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.

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