1. Unique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue
- Author
-
Ying Li, Yung-Chi Cheng, Chunxiao Ying, Michael D. Robek, and Chung-Hang Leung
- Subjects
Hepatitis B virus ,Time Factors ,Transcription, Genetic ,RNA Stability ,Down-Regulation ,Biology ,medicine.disease_cause ,Antiviral Agents ,Models, Biological ,Lignans ,Virus ,Cell Line ,Viral Proteins ,chemistry.chemical_compound ,Hepatocyte Nuclear Factors ,medicine ,Humans ,Benzodioxoles ,Promoter Regions, Genetic ,Enhancer ,Transcription factor ,Multidisciplinary ,Cell Death ,DNA replication ,virus diseases ,Promoter ,Biological Sciences ,Virology ,Molecular biology ,digestive system diseases ,Hepatocyte nuclear factor 4 ,chemistry ,Lamivudine ,Xanthines ,DNA, Viral ,Phthalazines ,RNA, Viral ,Thermodynamics ,DNA ,Protein Binding - Abstract
Helioxanthin is a natural product that inhibits the replication of a number of viruses. We found that a previously undescribed helioxanthin analogue, 8-1, exhibited potent anti-hepatitis B virus (HBV) activity with little cytotoxicity. 8-1 suppressed both HBV RNA and protein expression, as well as DNA replication of both wild-type and 3TC-resistant virus. Time-course analyses revealed that RNA expression was blocked first after treatment with 8-1, followed by viral proteins, and then DNA. 8-1 inhibited the activity of all HBV promoters by decreasing the binding of hepatocyte nuclear factor 4 (HNF-4), HNF-3, and fetoprotein factor to the precore/core promoter enhancer II region. The amount of HNF-4 and HNF-3 was decreased posttranscriptionally by 8-1 in HBV-producing cells, but not in HBV-negative cells. Therefore, 8-1 suppresses HBV replication by posttranscriptional down-regulation of critical transcription factors in HBV-producing cells, thus diminishing HBV promoter activity and blocking viral gene expression and replication. This mechanism is unique and different from other anti-HBV compounds previously described.
- Published
- 2007