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The Functional and Antiviral Activity of Interferon Alpha-Inducible IFI6 Against Hepatitis B Virus Replication and Gene Expression
The Functional and Antiviral Activity of Interferon Alpha-Inducible IFI6 Against Hepatitis B Virus Replication and Gene Expression
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 12 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- Hepatitis B virus is an enveloped DNA virus, that infects more than three hundred and sixty million people worldwide and leads to severe chronic liver diseases. Interferon-alpha inducible protein 6 (IFI6) is an IFN-stimulated gene (ISG) whose expression is highly regulated by the stimulation of type I IFN-alpha that restricts various kinds of virus infections by targeting different stages of the viral life cycle. This study aims to investigate the antiviral activity of IFI6 against HBV replication and gene expression. The IFI6 was highly induced by the stimulation of IFN-α in hepatoma cells. The overexpression of IFI6 inhibited while knockdown of IFI6 elevated replication and gene expression of HBV in HepG2 cells. Further study determined that IFI6 inhibited HBV replication by reducing EnhII/Cp of the HBV without affecting liver enriched transcription factors that have significant importance in regulating HBV enhancer activity. Furthermore, deletion mutation of EnhII/Cp and CHIP analysis revealed 100 bps (1715-1815 nt) putative sites involved in IFI6 mediated inhibition of HBV. Detailed analysis with EMSA demonstrated that 1715-1770 nt of EnhII/Cp was specifically involved in binding with IFI6 and restricted EnhII/Cp promoter activity. Moreover, IFI6 was localized mainly inside the nucleus to involve in the anti-HBV activity of IFI6. In vivo analysis based on the hydrodynamic injection of IFI6 expression plasmid along with HBV revealed significant inhibition of HBV DNA replication and gene expression. Overall, our results suggested a novel mechanism of IFI6 mediated HBV regulation that could develop potential therapeutics for efficient HBV infection treatment.
- Subjects :
- 0301 basic medicine
lcsh:Immunologic diseases. Allergy
Gene Expression Regulation, Viral
Male
Hepatitis B virus
030106 microbiology
Immunology
IFI6
Biology
medicine.disease_cause
Virus Replication
EMSA
Virus
Mitochondrial Proteins
03 medical and health sciences
Viral Proteins
interferon-stimulated genes
Gene expression
medicine
HBV
Animals
Humans
Immunology and Allergy
Enhancer
Promoter Regions, Genetic
Gene
Original Research
Gene knockdown
Expression vector
Binding Sites
CHIP
virus diseases
Interferon-alpha
DNA virus
Hep G2 Cells
Hepatitis B
Virology
digestive system diseases
Mice, Inbred C57BL
030104 developmental biology
HEK293 Cells
Liver
Host-Pathogen Interactions
antiviral activity
lcsh:RC581-607
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....0b76eb008c2d710bd3a16ba4d53135b3
- Full Text :
- https://doi.org/10.3389/fimmu.2021.634937