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Using Click Chemistry to Measure the Effect of Viral Infection on Host-Cell RNA Synthesis
Published on: August 9, 2013
Cell-specific proteins regulate viral RNA translation and virus-induced disease
E V Pilipenko1, E G Viktorova, S T Guest
1Department of Neurology, University of Chicago Medical Center, Chicago, IL 60637, USA. epilipen@neurology.bsd.uchicago.edu
The EMBO Journal
|December 1, 2001
Summary
Neural cells use a specific protein homologue (nPTB) for picornavirus translation initiation via the internal ribosome entry site (IRES). Differential binding of PTB and nPTB impacts viral neurovirulence.
Area of Science:
- Virology
- Molecular Biology
- Neuroscience
Background:
- Picornavirus translation initiation depends on internal ribosome entry sites (IRES).
- The GDVII virus IRES requires polypyrimidine tract-binding protein (PTB).
- Neural cells express a PTB homologue, nPTB, and have low PTB levels.
Purpose of the Study:
- To investigate the roles of PTB and nPTB in GDVII IRES function.
- To determine how differential binding affects translation initiation and viral neurovirulence.
Main Methods:
- RNA binding assays to assess PTB and nPTB interactions with the GDVII IRES.
- Mutagenesis of IRES binding sites.
- In vitro translation assays.
- Viral neurovirulence and growth assays in neural and non-neural cells.
Main Results:
- PTB and nPTB bind similarly to multiple sites in the GDVII IRES.
- Mutations affecting PTB/nPTB binding sites reduced nPTB binding more significantly than PTB binding.
- nPTB showed reduced activity compared to PTB in promoting translation initiation.
- Mutant viruses exhibited attenuated neurovirulence without affecting growth in non-neural cells.
- A second-site mutation restoring nPTB binding also restored translation and neurovirulence.
Conclusions:
- Tissue-specific expression and differential RNA-binding of PTB and nPTB are key regulators of cell-specific translation.
- These factors significantly influence picornavirus neurovirulence.
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