Program in Molecular Medicine
Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Cells | Digestive System | Digestive System Diseases | Enzymes and Coenzymes | Genetic Phenomena | Immunology and Infectious Disease | Neoplasms | Nucleic Acids, Nucleotides, and Nucleosides | Virus Diseases | Viruses
Certain organs are capable of containing the replication of various types of viruses. In the liver, infection of Hepatitis B virus (HBV), the etiological factor of Hepatitis B and hepatocellular carcinoma (HCC), often remains asymptomatic and leads to a chronic carrier state. Here we investigated how hepatocytes contain HBV replication and promote their own survival by orchestrating a translational defense mechanism via the stress-sensitive SUMO-2/3-specific peptidase SENP3. We found that SENP3 expression level decreased in HBV-infected hepatocytes in various models including HepG2-NTCP cell lines and a humanized mouse model. Downregulation of SENP3 reduced HBV replication and boosted host protein translation. We also discovered that IQGAP2, a Ras GTPase-activating-like protein, is a key substrate for SENP3-mediated de-SUMOylation. Downregulation of SENP3 in HBV infected cells facilitated IQGAP2 SUMOylation and degradation, which leads to suppression of HBV gene expression and restoration of global translation of host genes via modulation of AKT phosphorylation. Thus, The SENP3-IQGAP2 de-SUMOylation axis is a host defense mechanism of hepatocytes that restores host protein translation and suppresses HBV gene expression.
Hepatitis B virus, Immunoblotting, Messenger RNA, Virus effects on host gene expression, Hepatocytes, Protein translation, Gene expression, SUMOylation
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Copyright: © 2019 Xi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2019 Jan 14;14(1):e0209179. doi: 10.1371/journal.pone.0209179. eCollection 2019. Link to article on publisher's site
Xi R, Liu B, Han Y, Shen X. (2019). SENP3-mediated host defense response contains HBV replication and restores protein synthesis. Open Access Articles. https://doi.org/10.1371/journal.pone.0209179. Retrieved from https://escholarship.umassmed.edu/oapubs/3718
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This work is licensed under a Creative Commons Attribution 4.0 License.
Amino Acids, Peptides, and Proteins Commons, Biochemistry, Biophysics, and Structural Biology Commons, Cells Commons, Digestive System Commons, Digestive System Diseases Commons, Enzymes and Coenzymes Commons, Genetic Phenomena Commons, Immunology and Infectious Disease Commons, Neoplasms Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons, Virus Diseases Commons, Viruses Commons