Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis
Abstract
:1. Introduction
2. The Hepatitis C Virus (HCV)
3. Nuclear Factor Erythroid 2 (NF-E2)-Related Factor 2 (Nrf2)
3.1. Domain Structure of Nrf2
3.2. Nrf2 Regulation
3.2.1. Canonical Nrf2 Activation
Keap1-Mediated Activation of Nrf2
βTrCP-Mediated Activation of Nrf2
Hrd1-Mediated Activation of Nrf2
3.2.2. Non-Canonical Nrf2 Activation
4. Autophagy
5. Reactive Oxygen Species (ROS) in HCV-Infected Cells
6. Interference of HCV with the Nrf2/Keap1-Signaling Pathway
7. Impact of ROS in HCV-Associated Pathogenesis
8. The Hepatitis B Virus (HBV)
9. Generation of ROS in HBV-Replicating Cells
10. Interference of HBV with the Nrf2/Antioxidant Response Element (ARE) System
11. HBV Regulatory Proteins
12. Effect of ROS on the HBV Life-Cycle
13. ROS, Nrf2 and the Virus-Associated Pathogenesis
14. Liver Regeneration
15. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AhR | aryl hydrocarbon receptor |
AKT | protein kinase B |
AMPK | AMP-activated protein kinase |
AMPKα | AMP-activated protein kinaseα |
AP-1 | activating protein 1 |
ARE | antioxidant-response element |
ATF6 | activating transcription factor 6 |
Atg | autophagy-regulated genes |
Bach1/2 | BTB and CNC homology 1/2 |
BCLN1 | Beclin1 |
BRCA1 | breast cancer type 1 susceptibility protein |
BTB | Broad-Complex, Tramtrack and Bric a brac |
bZIP | basic-region leucine zipper |
cat | catalase |
CBP | CREB (cAMP response element-binding protein)-binding protein |
CDH6 | chromo-ATPase/ helicase DNA-binding domain 6 |
CHC | chronic hepatitis C |
CK2 | casein kinase 2 |
CNC | cap´n´collar |
COX | cytochrome c oxidase |
CTGF | connective tissue growth factor |
CYP2E1 | cytochrome P450 2E1 |
DAA | direct-acting antivirals |
DFCP1 | double FYVE-containing protein 1 |
DMV | double membrane vesicle |
DNMTA3 | DNA methyltransferase |
DPP3 | dipeptidyl peptidase III |
ECM | extracellular matrix |
EGF | epidermal growth factor |
EGFR | epidermal growth factor receptor |
ephx1 | epoxide hydrolase 1 |
EpRE | electrophile-response element |
ER | endoplasmatic reticulum |
ERK | extracellular signal-regulated kinase |
Ero1α | ER oxidoreductin 1α |
ERQC | ER protein quality control |
FGF | fibroblast growth factor |
GABARAP | gamma-aminobutyric acid receptor-associated protein participate |
GCLC | glutamate-cysteine ligase catalytic subunit |
GLUT4 | glucose transporter 4 |
GPx | glutathione peroxidase |
GSH | glutathione |
GSK3β | glycogen synthase kinase 3β |
GSTM3 | glutathione-S-transferase M3 |
GSTP1 | glutathione-S-transferase P1 |
HBsAg | surface antigen |
HBV | hepatitis B virus |
HCC | hepatocellular carcinoma |
HCV | hepatitis C virus |
HO-1 | heme oxygenase-1 |
HSC | hepatic stellate cells |
IGF-I | insulin-like growth factor I |
IL-6 | interleukin 6 |
IM | isolation membrane |
IRE1 | inositol-required protein 1 |
IRES | internal ribosomal entry site |
JAK2 | Janus kinase 2 |
JNK | c-Jun-N-terminal kinase |
Keap1 | Kelch-like Ech-associated protein 1 |
KIR | Keap1-interacting region |
LC3 | microtubule-associated protein 1 light chain 3 |
LD | lipid droplets |
LHBs | large HBV surface protein |
LIR | LC3 interacting region |
LPS | lipopolysaccharide |
LVP | lipoviroparticle |
MAM | mitochondrial-associated membrane |
MAPK | mitogen activated protein kinase |
MCU | mitochondrial Ca2+-uniporter |
MEF2D | myocyte enhancer factor 2d |
MEOS | microsomal ethanol oxidizing enzymes |
MHBs | middle surface |
MPT | mitochondrial permeability transition |
mPTP | mitochondrial permeability transition pore |
mTORC1 | mammalian target of rapamycin complex 1 |
MVBs | multivesicular bodies |
MW | membranous web |
NAC | N-acetylcysteine |
Neh | Nrf2-Ech homology |
NF-κB | nuclear factor κB |
NOX | NADPH oxidases |
NQO1 | NAD(P)H quinone oxidoreductase 1 |
Nrf1 | NF-E2 related factor 1 |
Nrf2 | nuclear factor erythroid 2 (NF-E2)-related factor 2 |
NS | non-structural |
ObR | obese receptor |
OGG1 | 8-oxoguanine glycosylase 1 |
PALB2 | partner and localizer for BRCA2 |
PAS | phagophore assembly sites |
PCK2 | phosphoenolpyruvate carboxykinase 2 |
PDGF | platelet derived growth factor |
PDI | protein disulfide isomerase |
PE | phosphatidylethanolamine |
PERK | protein kinase (PKR)-like ER kinase |
PGC1α | peroxisome proliferator-activated receptor-gamma co-activator 1α |
PI3K | phosphatidylinositol 3-kinase |
PI3P | phosphatidylinositol-3-phosphate |
PI4K4 | phosphatidylinositol 4-kinase IIIα |
PKB | phosphatidylinositol 3-kinase (PI3K) kinase B |
PKC | protein kinase C |
PM | plasma membrane |
PPARγ | peroxisome proliferator-activated receptor γ |
ProTα | Prothymosin α |
Rac | receptor-associated coactivator |
ROS | reactive oxygen species |
RXRα | retinoid X receptor α |
SERCA | sarcoplasmic/endoplasmic reticulum calcium ATPase 2 |
SHBs | proteinsmall surface protein |
Skp1 | S-phase kinase-associated protein 1 |
sMaf | v-maf avian musculoaponeurotic fibrosarcoma |
SOCS3 | suppressor of cytokine signaling 3 |
SOD2 | superoxide dismutase |
SQSTM1 | sequestome 1 |
β-TrCP | β-transducin repeat-containing protein |
STAT3 | signal transducer and activator of transcription 3 |
SUMO | small ubiquitin-like modifier |
TAK1 | transforming growth factor β-activated kinase1 |
TBK-1 | TANK-binding kinase 1 |
tg | transgenic |
TGF-β1 | transforming growth factor beta-1 |
TNF-α | tumor necrosis factor α |
TRAMP | transgenic adenocarcinoma of mouse prostate |
TRIM16 | tripartite motif containing 16 |
TSC | tuberous sclerosis complex |
UBA | ubiquitin-associated |
ULK1 | Unc-51-like kinase 1 |
UPR | unfolded protein response |
UTR | untranslated region |
VDAC3 | voltage-dependent anion channel 3 |
VLDL | very-low-density lipoprotein |
Vps34 | vacuolar protein sorting 34 |
WIPI | WD-repeat domain phosphoinositide-interacting |
WTX | Wilms tumor gene in chromosome X |
XBP1 | X box-binding protein 1 |
XRE | xenobiotic response element |
γ-GCS | γ-glutamylcysteine synthetase |
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Bender, D.; Hildt, E. Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis. Int. J. Mol. Sci. 2019, 20, 4659. https://doi.org/10.3390/ijms20184659
Bender D, Hildt E. Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis. International Journal of Molecular Sciences. 2019; 20(18):4659. https://doi.org/10.3390/ijms20184659
Chicago/Turabian StyleBender, Daniela, and Eberhard Hildt. 2019. "Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis" International Journal of Molecular Sciences 20, no. 18: 4659. https://doi.org/10.3390/ijms20184659