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Purification of Viral DNA for the Identification of Associated Viral and Cellular Proteins
Published on: August 31, 2017
The Host Cell Factor Phosphatase-2A Subunit PR130 Restricts Replication of Herpes Simplex Virus Type-1
Johannes Jungwirth1,2, Christoph F Jacob1, Alexandra Nguyen2
1Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Jena, Germany.
Protein phosphatase 2A (PP2A) subunit PR130 suppresses herpes simplex virus type-1 (HSV-1) replication by regulating cell cycle and DNA repair proteins. HSV-1 infection reduces PR130, impacting viral replication.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Herpes simplex virus type-1 (HSV-1) infects over 60% of the population and poses challenges due to antiviral resistance.
- HSV-1 replication relies on host deoxynucleotides and manipulation of cellular DNA processes.
Purpose of the Study:
- To identify host factors that regulate HSV-1 replication.
- To investigate the role of protein phosphatase 2A (PP2A) regulatory subunit PR130 (PPP2R3A) in HSV-1 infection.
Main Methods:
- Global proteome and phosphoproteome profiling.
- Functional assays in epithelial and neuronal cells.
- Analysis of cell cycle and DNA repair pathways.
Main Results:
- PR130 suppresses laboratory and clinical HSV-1 strains; HSV-1 infection decreases PR130 levels.
- PR130 modulates cell cycle regulators, including p21 (CDKN1A) phosphorylation by CDK2.
- PR130 depletion enhances ATM signaling and increases HSV-1 dependency on ATM.
Conclusions:
- PR130 is a key host factor suppressing HSV-1 replication.
- PR130 regulates p21 and ATM pathways, crucial for controlling HSV-1 infection.
- Targeting PR130 or associated pathways may offer new antiviral strategies.
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