Inhibition of HBV Transcription From cccDNA With Nitazoxanide by Targeting the HBx–DDB1 Interaction
説明
Hepatitis B virus (HBV) infection leads to chronic hepatitis B (CHB) in approximately 250 million people worldwide, putting them at high risk for developing cirrhosis and hepatocellular carcinoma. HBV is a partially double-stranded DNA virus that belongs to the Hepadnaviridae family. After entry into host cells, the viral genome is transported into the nucleus and converted to a covalently closed circular DNA (cccDNA), which serves as the template for all HBV viral RNAs. Currently available HBV antiviral drugs inhibit the reverse transcription of HBV pregenomic RNA but fail to suppress the established cccDNA reservoir in infected hepatocytes, resulting in viral rebound after therapy. In addition, HBV surface antigen hepatitis B surface antigen expressed from the cccDNA maintains immune tolerance to prevent induction of antibodies to hepatitis B surface antigen, which are critical for a functional cure of CHB in patients.
収録刊行物
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- Cellular and Molecular Gastroenterology and Hepatology
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Cellular and Molecular Gastroenterology and Hepatology 7 (2), 297-312, 2019
Elsevier BV
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キーワード
- DDB1, damage-specific DNA-binding protein 1
- Transcription, Genetic
- mcHBV, minicircle hepatitis B virus
- RC799-869
- DMSO, dimethyl sulfoxide
- Flag-HBx, Flag-tagged hepatitis B virus regulatory protein X
- Cluc, Cypridina luciferase
- LgBit, Large Bit
- Viral Regulatory and Accessory Proteins
- PSAD, plasmid-safe DNase
- HBx, hepatitis B virus regulatory protein X
- Original Research
- Smc5/6, structural maintenance of chromosomes 5/6
- DMEM, Dulbecco's modified Eagle's medium
- HBs, hepatitis B surface antibody
- IFNα, interferon alfa
- IP, immunoprecipitation
- Hep G2 Cells
- Diseases of the digestive system. Gastroenterology
- Nitro Compounds
- mRNA, messenger RNA
- DNA-Binding Proteins
- Editorial
- RNA, Viral
- qPCR, quantitative polymerase chain reaction
- DNA, Circular
- cccDNA, covalently closed circular DNA
- Protein Binding
- Hepatitis B virus
- SDS, sodium dodecyl sulfate
- Minicircle
- Humans
- RNA, Messenger
- Primary Hepatocyte Infection
- ddPCR, droplet digital polymerase chain reaction
- Gluc, Gaussia luciferase
- Drug Screening
- pgRNA, pregenomic RNA
- CMV, cytomegalovirus
- FDA, Food and Drug Administration
- High-Throughput Screening Assays
- Thiazoles
- HEK293 Cells
- HBV, hepatitis B virus
- NTZ, nitazoxianide
- DNA, Viral
- Proteolysis
- Hepatocytes
- Trans-Activators
- SmBit, Small Bit
詳細情報 詳細情報について
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- CRID
- 1360567182211353856
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- ISSN
- 2352345X
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE