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Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
Published on: April 25, 2018
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Polyprotein processing and intermolecular interactions within the viral replication complex spatially and temporally
Edward Emmott1, Alexis de Rougemont2,3, Myra Hosmillo4
1From the Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom, e.emmott@northeastern.edu.
The Journal of Biological Chemistry
|January 17, 2019
Summary
Norovirus protease precursors are active but their function is regulated by cellular localization and protein interactions. Understanding this regulation provides new targets for antiviral drug design against norovirus infections.
Area of Science:
- Virology
- Molecular Biology
- Drug Discovery
Background:
- Norovirus causes significant acute viral gastroenteritis globally.
- Norovirus replication relies on polyprotein processing by a viral protease.
- Protease precursor accumulation affects viral replication rates.
Purpose of the Study:
- Characterize norovirus protease precursor accumulation during infection.
- Investigate the activity and regulation of protease precursors in cells.
- Identify protein interactions influencing protease precursor localization and function.
Main Methods:
- Expression of stable protease precursor forms in cells.
- In vitro proteolytic activity assays.
- LUMIER assay for mapping protein-protein interactions.
- Analysis of substrate cleavage based on protease localization.
Main Results:
- All norovirus protease precursors are proteolytically active in vitro.
- Cellular localization and substrate availability determine precursor activity.
- Specific precursors lacking NS4 protein efficiently cleave cytoplasmic substrates.
- Conserved protein interactions regulate protease precursor localization.
Conclusions:
- Norovirus protease activity is regulated by localization and protein interactions.
- A model for regulated substrate cleavage during norovirus replication is proposed.
- Understanding protease regulation offers new antiviral drug design strategies.
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