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SENP3-mediated host defense response contains HBV replication and restores protein synthesis.
- Source :
-
PloS one [PLoS One] 2019 Jan 14; Vol. 14 (1), pp. e0209179. Date of Electronic Publication: 2019 Jan 14 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- 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.<br />Competing Interests: The co-authors Dr. Yan Han and Dr. Ji Wan are currently employed by CuraCloud Corporation, which had no role or any financial interest in the submitted manuscript. Their current employment does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents or products in development to declare. The other authors declare no competing interests.
- Subjects :
- Animals
Cysteine Endopeptidases genetics
Down-Regulation
Gene Expression Regulation, Viral
Gene Knockdown Techniques
Hep G2 Cells
Hepatitis B metabolism
Hepatitis B virology
Hepatitis B virus genetics
Hepatitis B virus pathogenicity
Host Microbial Interactions genetics
Humans
Mice
Mice, Transgenic
Models, Biological
Proto-Oncogene Proteins c-akt metabolism
Substrate Specificity
Sumoylation
Virus Replication physiology
ras GTPase-Activating Proteins antagonists & inhibitors
ras GTPase-Activating Proteins genetics
ras GTPase-Activating Proteins metabolism
Cysteine Endopeptidases metabolism
Hepatitis B virus physiology
Hepatocytes metabolism
Hepatocytes virology
Host Microbial Interactions physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 30640896
- Full Text :
- https://doi.org/10.1371/journal.pone.0209179