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Updated: Jun 11, 2025
09:10
siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
Published on: October 28, 2019
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The Autophagy Receptor SQSTM1/p62 Is a Restriction Factor of HCMV Infection
Nadine Krämer1, Uxía Gestal Mato2, Steffi Krauter1
1Institute for Virology and Forschungszentrum Immuntherapie, University Medical Center of the Johannes Gutenberg-University, 55131 Mainz, Germany.
Viruses
|September 28, 2024
Summary
The autophagy receptor sequestome 1 (p62) acts as a restriction factor against human cytomegalovirus (HCMV) infection. Phosphorylation enhances p62
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Intrinsic host defense mechanisms are crucial for early-stage viral infection control.
- The autophagy receptor sequestome 1 (SQSTM1/p62) role in human cytomegalovirus (HCMV) infection was investigated.
Purpose of the Study:
- To elucidate the mechanism by which p62 interferes with HCMV infection.
- To determine the role of p62 phosphorylation in regulating HCMV replication.
Main Methods:
- CRISPR/Cas9-mediated genome editing was employed to generate p62 knockout cells.
- Mass spectrometry and phosphoproteomics were utilized to identify protein interactions and phosphorylation sites.
- Recombinant HCMVs expressing p62 phosphovariants were generated to study functional consequences.
Main Results:
- p62 knockout led to increased HCMV progeny release, indicating a restriction role.
- Mass spectrometry identified p62 interaction with nucleocytoplasmic transport proteins.
- Hyperphosphorylation of p62 at S272 enhanced nuclear retention and interaction with viral proteins, reducing progeny release.
Conclusions:
- p62 functions as a restriction factor against HCMV replication.
- Phosphorylation at S272 regulates p62's nuclear localization and antiviral activity.
- p62-mediated viral protein degradation and impaired progeny production were observed.
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