SENP3-mediated host defense response contains HBV replication and restores protein synthesis

Autor: Yan Han, Shu-Bing Qian, Rui Xi, Anastasia Varanko, Yongning Xin, Xiaodong Li, Lishan Su, Preetish Kadur Lakshminarasimha Murthy, Cynthia D. Guy, Xiling Shen, Botao Liu, Nikolai Rakhilin, Zhuo Wang, Kuei Ling Tung, Ji Wan, Feng Li
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Host Defense Mechanism
SUMO protein
Gene Expression
medicine.disease_cause
Virus Replication
Biochemistry
Substrate Specificity
Mice
0302 clinical medicine
IQGAP2
Animal Cells
Pathology and laboratory medicine
Regulation of gene expression
Multidisciplinary
Messenger RNA
Hep G2 Cells
Medical microbiology
Hepatitis B
SUMOylation
3. Good health
Cell biology
Nucleic acids
Cysteine Endopeptidases
Liver
ras GTPase-Activating Proteins
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Viruses
Medicine
Post-translational modification
Pathogens
Cellular Types
Anatomy
Research Article
Gene Expression Regulation
Viral
Hepatitis B virus
Science
Immunoblotting
Down-Regulation
Molecular Probe Techniques
Mice
Transgenic
Biology
Research and Analysis Methods
Models
Biological
Microbiology
Virus Effects on Host Gene Expression
03 medical and health sciences
Downregulation and upregulation
Virology
medicine
Genetics
Animals
Humans
Molecular Biology Techniques
Gene
Molecular Biology
Medicine and health sciences
Host Microbial Interactions
Biology and life sciences
Viral pathogens
Organisms
Proteins
Cell Biology
Hepatitis viruses
digestive system diseases
Microbial pathogens
030104 developmental biology
Humanized mouse
Hepatocytes
RNA
Protein Translation
Proto-Oncogene Proteins c-akt
Zdroj: PLoS ONE, Vol 14, Iss 1, p e0209179 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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