Back to Search
Start Over
Unique antiviral mechanism discovered in anti-hepatitis B virus research with a natural product analogue.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 5/15/2007, Vol. 104 Issue 20, p8526-8531. 6p. 1 Chart, 6 Graphs. - Publication Year :
- 2007
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HEPATITIS B virus
*HEPATITIS viruses
*RNA
*DNA
*LIVER cells
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 104
- Issue :
- 20
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 25301042
- Full Text :
- https://doi.org/10.1073/pnas.0609883104