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Selective Polyprotein Processing Determines Norovirus Sensitivity to Trim7
Meagan E Sullender1, Linley R Pierce2, Mridula Annaswamy Srinivas2
1Division of Infectious Diseases, Department of Medicine, Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, Missouri, USA.
Journal of Virology
|August 16, 2022
Summary
Murine norovirus (MNV) evades host restriction by the antiviral protein Trim7 through selective polyprotein processing. This evasion strategy comes at a significant evolutionary cost, attenuating viral replication and pathogenesis.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Noroviruses cause widespread gastroenteritis, but host restriction mechanisms remain unclear.
- Understanding host-pathogen interactions is crucial for combating viral infections.
Purpose of the Study:
- Identify host genes restricting murine norovirus (MNV) replication using CRISPR activation.
- Investigate the role of Trim7 in inhibiting MNV infection and viral evasion strategies.
Main Methods:
- CRISPR activation screen to identify host restriction factors.
- In vitro evolution to generate and study viral escape mutants.
- Biochemical assays to analyze protein-protein interactions and polyprotein processing.
Main Results:
- Trim7 potently inhibits early MNV replication.
- MNV mutants escaping Trim7 restriction alter NS6-7 polyprotein cleavage.
- Trim7 binds viral protein NS6, but not the NS6-7 precursor.
- Altered polyprotein processing for Trim7 evasion significantly attenuates viral fitness.
Conclusions:
- Selective polyprotein processing is a novel viral immune evasion mechanism.
- Viral resistance to host restriction factors involves evolutionary trade-offs.
- Findings offer insights into norovirus-host interactions and viral evolution.
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