Interplay between Cellular Autophagy and Hepatitis B Virus Replication: A Systematic Review
Abstract
:1. Introduction
2. HBV-Mediated Autophagic Responses
2.1. HBV Induces the Initiation of Autophagy
2.2. HBV Promotes Phagophore Formation
2.3. HBV Activates Phagophore Expansion and Forms Autophagosomes
2.4. HBV Interferes with Autophagic Degradation
3. Autophagy-Mediated HBV Replication and Assembly
3.1. HBV Manipulates Autophagic Components for Its Replication
3.2. HBV Utilizes Autophagic Elements for its Envelopment
3.3. Late Autophagy Degrades HBV NCs/Virions and SVPs
3.4. HBV Evades Cell Death via HBX-Induced Autophagy for Persistent Infection
3.5. Autophagy Regulates HBV-Related Immune Responses
4. Autophagy-Based Anti-HBV Strategies
5. Conclusions and Perspective
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AMPK | AMP-protein activated kinase |
ATG | Autophagy-related gene |
BECN1 | Beclin 1 |
HBV | Hepatitis B virus |
HBeAg | Hepatitis B e antigen |
MAP1LC3/LC3 | Microtubule-associated protein 1 light chain 3 |
mTOR | Mammalian target of rapamycin |
NC | Nucleocapsid |
ORF | Open reading frame |
PtdIns3K | Class III phosphatidylinositol 3-kinase |
siRNA | Small interfering RNA |
SVP | Subviral particle |
ULK1 | Unc-51 like autophagy activating kinase 1 |
UPR | Unfolded protein response |
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HBV Proteins. | Models | Mechanisms | Effects | References |
---|---|---|---|---|
HBx | HepG2.2.15 and HepAD38 cells | Activate AMPK by ROS accumulation | Induce autophagy initiation (?) | [14] |
Promote autophagic degradation | ||||
HBx | Primary rat hepatocytes; HepG2.2.15 cells and primary hepatocytes | Activate AMPK signaling | Induce autophagy initiation | [34,36] |
HBx | L02, Chang, HepG2, and BEL-7404 cells | Directly transactivates BECN1 promoter activity and upregulates its expression during starvation | Promote phagophore formation | [11] |
HBx | Chang cells | Increase the activity of DAPK in a BECN1-associated pathway | Promote phagophore formation | [12] |
SHBs | Huh7 cells | Activate IRE1α/XBP1/BECN1 axis | Promote phagophore formation | [13,37] |
HBx | Huh7.5 cells | Directly bind to PtdIns3K and enhance its enzymatic activity | Promote phagophore formation | [38] |
HBx | HepG2 cells | Dissociate BECN1 and Bcl-2 via the ROS/JNK signaling pathway | Promote phagophore formation | [39] |
HBx | HepG2.2.15 and Huh7 cells; primary human hepatocytes; hydrodynamic-based HBV mouse model | Activate BECN1-mediated autophagy through C-myc/miR-192-3p/XIAP/NF-κB axis | Promote phagophore formation | [40] |
SHBs | Huh7 cells | Activate PERK/eIF2α and ATF6/GRP78/94 signaling to enhance their interaction with the autophagy-associated proteins ATG5, ATG12, and/or ATG16L | Activate phagophore expansion and form autophagosomes | [13,37] |
HBx | Huh7 cells | Impair lysosome maturation by inhibiting its acidification | Interfere with autophagic degradation | [16] |
HBV | HepG2.2.15 and Huh7 cells | Block the fusion of autophagosomes with lysosomes by decreasing the expression of Rab7 and SNAP29 | Interfere with autophagic degradation | [18,21,41] |
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Lin, Y.; Zhao, Z.; Huang, A.; Lu, M. Interplay between Cellular Autophagy and Hepatitis B Virus Replication: A Systematic Review. Cells 2020, 9, 2101. https://doi.org/10.3390/cells9092101
Lin Y, Zhao Z, Huang A, Lu M. Interplay between Cellular Autophagy and Hepatitis B Virus Replication: A Systematic Review. Cells. 2020; 9(9):2101. https://doi.org/10.3390/cells9092101
Chicago/Turabian StyleLin, Yong, Zhenyu Zhao, Ailong Huang, and Mengji Lu. 2020. "Interplay between Cellular Autophagy and Hepatitis B Virus Replication: A Systematic Review" Cells 9, no. 9: 2101. https://doi.org/10.3390/cells9092101