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ATP1B3 cooperates with BST‐2 to promote hepatitis B virus restriction
- Source :
- Journal of Medical Virology
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Increasing evidence indicates ATP1B3, one of the regulatory subunits of Na+/K+‐ATPase, is involved in numerous viral propagations, such as HIV and EV71. However, the function and mechanism of ATP1B3 on hepatitis B virus (HBV) propagation is unknown. Here, we demonstrated that ATP1B3 overexpression reduced the quantity of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in supernatants of HBV expression plasmids cotransfected HepG2 cells. Correspondingly, small interfering RNA and short hairpin RNA mediated ATP1B3 silencing promoted HBsAg and HBeAg expression in the supernatants of HBV expression plasmids transfected HepG2 cells. Mechanically, we reported that ATP1B3 expression could activate nuclear factor‐κB (NF‐κB) pathway by inducing the expression, phosphorylation, and nuclear import of P65 for the first time. And NF‐κB inhibitor (Bay11) impaired the restraint of ATP1B3 on HBV replication. This counteraction effect of Bay11 proved that ATP1B3‐induced NF‐κB activation was crucial for HBV restriction. Accordingly, we observed that anti‐HBV factors interferon‐α (IFN‐α) and interleukin‐6 (IL‐6) production were increased in HepG2 cells after the NF‐κB activation. It suggested that ATP1B3 suppressed HBsAg and HBeAg by NF‐κB/IFN‐α and NF‐κB/IL‐6 axis. Further experiments proved that ATP1B3 overexpression induced anti‐HBV factor BST‐2 expression by NF‐κB/IFN‐α axis in HepG2 cells but not HEK293T cells, and ATP1B3 silencing downregulated BST‐2 messenger RNA level in HepG2 cells. As an HBV restriction factor, BST‐2 cooperated with ATP1B3 to antagonize HBsAg but not HBeAg in HepG2 cells. Our work identified ATP1B3 as a novel candidate of HBV restrictor with unrevealed mechanism and we highlighted it might serve as a potential therapeutic molecule for HBV infection.<br />Highlight ATP1B3 suppressed HBV replication by NF‐κB/IFN‐α and NF‐κB/IL6 axis.ATP1B3 induced anti‐HBV factor BST‐2 expression by NF‐κB/IFN‐α axis.BST‐2 cooperated with ATP1B3 to antagonize HBsAg but not HBeAg expression in vitro.
- Subjects :
- Gene Expression Regulation, Viral
Hepatitis B virus
HBsAg
Small interfering RNA
Cell Survival
ATP1B3
GPI-Linked Proteins
Virus Replication
medicine.disease_cause
Small hairpin RNA
03 medical and health sciences
0302 clinical medicine
Antigens, CD
Interferon
Virology
HBV
2',5'-Oligoadenylate Synthetase
medicine
Humans
Gene silencing
Hepatitis B e Antigens
030212 general & internal medicine
Ubiquitins
Research Articles
IFN‐α
Adaptor Proteins, Signal Transducing
Hepatitis B Surface Antigens
Chemistry
NF‐κB
BST‐2
NF-kappa B
Interferon-alpha
RNA-Binding Proteins
virus diseases
Hep G2 Cells
Transfection
digestive system diseases
HEK293 Cells
Infectious Diseases
HBeAg
Cytokines
030211 gastroenterology & hepatology
Sodium-Potassium-Exchanging ATPase
Research Article
Transcription Factors
medicine.drug
Subjects
Details
- ISSN :
- 10969071 and 01466615
- Volume :
- 92
- Database :
- OpenAIRE
- Journal :
- Journal of Medical Virology
- Accession number :
- edsair.doi.dedup.....12408afcc4780ae1579e13ffd72e30ad