The Interactions Between HBV and the Innate Immunity of Hepatocytes
Abstract
:1. Introduction
2. Genetic Organization, Life Cycle, and Global Epidemiology of HBV
3. HBV Infection and Host Innate Immunity
3.1. Hepatitis B e Antigen (HBeAg)
3.2. HBV Core Protein (HBcAG) and Hepatitis B Splice Protein (HBSP)
3.3. Hepatitis B Virus X Protein (HBx)
3.4. Hepatitis B Virus Polymerase Inhibits Innate Immunity (HBV Pol)
4. Conflicts Regarding HBV and Innate Immunity
5. In Vitro Models to Study HBV Infection and Innate Immunity
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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HBV Proteins | Cellular Innate Immunity Targets | References |
---|---|---|
Polymerase | RIG-I, TLR3/TBK1, IKKɛ, DDX3/IFN-β, IFN/JAK-STAT | [45,46,47] |
Hepatitis B virus X protein | RIG-I, melanoma differentiation-associated gene 5 (MDA5)/MAVS/IFN-β/Trim22 | [40,41,48,49] |
Core/precore | IFN/myxovirus resistance A (MxA) | [50] |
Hepatitis B e antigen | TLR2/ MyD88-Adapter-Like (MAL) | [51,52] |
Cell Models | HBV Infection Efficiency | Innate Immunity Pathways Present | Advantages Limitations | References |
---|---|---|---|---|
Primary human hepatocytes (PHHs) | Average 50% in the presence of 5% polyethylene glycol (PEG) | Low TLR expression | Gold standard for investigation of HBV infection; limited availability and unpredictable variability | [77,78,79] |
Low stimulator of interferon genes(STING) expression | ||||
RIG-I/MDA5 | ||||
NF-κB pathway | ||||
IRF pathway | ||||
IFN pathway | ||||
Human embryonic stem cell (hESC)/human induced-pluripotent stem cell (hiPSC)-derived hepatocytes | 25–90% | Low TLR expression | Close to PHHs depending on differentiation status; can support long-term infection, can be generated from donors with different genetic backgrounds; immature status needs to be improved | [72,76,80,81,82] |
Low STING expression | ||||
NF-κB pathway | ||||
IRF pathway | ||||
IFN pathway | ||||
HepaRG | ~10% in the presence of PEG, maximum rate is 20% | Low TLR expression | Close to PHHs; | [78,79,83,84] |
Low STING expression | suitable for drug metabolism and HBV infection; can be differentiated into both biliary cells and hepatocytes; a long period for differentiation is needed (at least two weeks) | |||
RIG-I/MDA5 | ||||
NF-κB pathway | ||||
IRF pathway | ||||
IFN pathway | ||||
HepG2-NTCP | ~70% infection efficiency at 4% PEG and 2.5% dimethyl sulfoxide (DMSO) | Poorly characterized | Can be used to screen novel drugs and elucidate host–virus interaction; high concentrations of HBV genome equivalents are needed for a high infection rate | [37,64,65,79,85,86,87,88,89,90] |
TLR expression | ||||
No cyclic GMP-AMP synthase (cGAS) | ||||
expression and low STING expression | ||||
RIG-I/MDA5 | ||||
NF-κB pathway | ||||
IRF pathway | ||||
IFN pathway | ||||
Huh7-NTCP | ~5% infection efficiency at 4% PEG and 2.5% DMSO | Poorly characterized | Low HBV infection rate; defects in some innate immunity pathways | [37,64,65,79,88,89,90] |
TLR expression | ||||
No cGAS and STING expression | ||||
Both RIG-I/MDA-5 and IFN pathway are present but weaker than HepG2 | ||||
HepG2.2.15 | HBV genome integrated the into HepG2 genome | No cGAS expression and low | Can be used to screen anti-HBV drugs Unsuitable for studying HBV entry and uncoating | [37,62,86,87,91,92] |
STING expression | ||||
RIG-I/MDA5 | ||||
NF-κB pathway | ||||
IRF pathway | ||||
IFN pathway |
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Megahed, F.A.K.; Zhou, X.; Sun, P. The Interactions Between HBV and the Innate Immunity of Hepatocytes. Viruses 2020, 12, 285. https://doi.org/10.3390/v12030285
Megahed FAK, Zhou X, Sun P. The Interactions Between HBV and the Innate Immunity of Hepatocytes. Viruses. 2020; 12(3):285. https://doi.org/10.3390/v12030285
Chicago/Turabian StyleMegahed, Fayed Attia Koutb, Xiaoling Zhou, and Pingnan Sun. 2020. "The Interactions Between HBV and the Innate Immunity of Hepatocytes" Viruses 12, no. 3: 285. https://doi.org/10.3390/v12030285