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Endoplasmic Reticulum-Associated Degradation Controls Virus Protein Homeostasis, Which Is Required for Flavivirus
Keisuke Tabata1,2, Masashi Arakawa3, Kotaro Ishida3
1Laboratory of Intracellular Membrane Dynamics, Graduate School of Frontier Biosciences Osaka University, Osaka, Japan.
Journal of Virology
|May 13, 2021
Summary
Viral protein homeostasis is maintained by the endoplasmic reticulum-associated degradation (ERAD) pathway, specifically involving Derlin2 and SEL1L. This process degrades excess nonstructural (NS) viral proteins within the convoluted membrane (CM), crucial for viral propagation.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Positive-stranded RNA viruses produce viral proteins via polyprotein processing.
- This process leads to stoichiometric imbalances, as viral protein requirements vary.
- Excess viral proteins can disrupt cellular processes and viral replication.
Purpose of the Study:
- To investigate the degradation mechanism of excess nonstructural (NS) viral proteins.
- To identify the role of endoplasmic reticulum-associated degradation (ERAD) in viral protein homeostasis.
- To determine the specific ERAD components involved in Japanese encephalitis virus and dengue virus replication.
Main Methods:
- Gene targeting studies to assess the role of ERAD components.
- Localization studies of Derlin2 within viral replication organelles.
- Analysis of viral NS protein degradation in the convoluted membrane (CM).
Main Results:
- Excess membrane-anchored NS proteins of Japanese encephalitis virus and dengue virus are degraded by ERAD.
- Derlin2 and SEL1L, but not Derlin1, are essential for viral genome replication.
- Derlin2 localizes to the CM, where viral NS proteins are degraded.
Conclusions:
- Derlin2-mediated ERAD in the CM regulates viral protein homeostasis, critical for viral propagation.
- The convoluted membrane (CM) acts as a site for viral protein degradation.
- The Derlin2/SEL1L/HRD1 pathway is involved, highlighting a novel ERAD-mediated fine-tuning system for viral proteins.
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