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Updated: Dec 9, 2025
09:10
siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
Published on: October 28, 2019
7.6K
O-GlcNAcylation modulates HBV replication through regulating cellular autophagy at multiple levels.
Xueyu Wang1, Yong Lin1,2, Shi Liu1,3
1Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Summary
Decreased O-GlcNAcylation enhances hepatitis B virus (HBV) replication by disrupting cellular autophagy. Inhibition of O-linked-N-acetylglucosamine (O-GlcNAc) transferase (OGT) promotes viral replication and protein production.
Area of Science:
- Biochemistry
- Virology
- Cellular Biology
Background:
- O-GlcNAcylation is a crucial posttranslational modification regulating protein function.
- Cellular autophagy plays a role in hepatitis B virus (HBV) replication and assembly.
- O-linked-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation.
Purpose of the Study:
- To investigate the regulatory role of O-GlcNAcylation in cellular autophagy and HBV replication.
- To elucidate the mechanisms by which O-GlcNAcylation influences HBV propagation.
Main Methods:
- Inhibition of OGT activity using the small molecule inhibitor OSMI-1.
- Silencing of OGT expression via genetic methods.
- Western blotting to analyze protein levels and autophagic markers (LC3-II, SQSTM1/p62).
- Assessment of endoplasmic reticulum (ER) stress and autophagosome-lysosome fusion.
Main Results:
- Inhibition of OGT significantly enhanced HBV replication and HBsAg production in hepatoma cells and primary human hepatocytes (PHHs).
- Decreased O-GlcNAcylation induced ER stress and autophagy, leading to increased HBV replication.
- Autophagosome formation and levels of autophagic markers were elevated upon OGT inhibition.
- Autophagosome-lysosome fusion was blocked, impairing autophagic degradation of HBV components.
- OSMI-1 promoted autophagosome formation by inhibiting Akt and mTOR O-GlcNAcylation.
Conclusions:
- Decreased O-GlcNAcylation promotes HBV replication by upregulating autophagosome formation through multiple pathways.
- These pathways include ER-stress induction, Akt/mTOR inhibition, and blockade of autophagosome-lysosome fusion.
- Targeting O-GlcNAcylation represents a potential strategy for controlling HBV replication.
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