The Alkylated Imino Sugar, n -( n -Nonyl)-Deoxygalactonojirimycin, Reduces the Amount of Hepatitis B Virus Nucleocapsid in Tissue Culture
| Autor: | Timothy M. Block, Ender Simsek, Xuanyong Lu, Trang Tran |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Hepatitis B virus
Immunoprecipitation Immunology Replication medicine.disease_cause Antiviral Agents Microbiology Cell Line Tissue culture Transcription (biology) Interferon Virology Centrifugation Density Gradient medicine Humans Phosphorylation Nucleocapsid Polymerase Glucosamine biology Viral Core Proteins Galactose Transfection Molecular biology Imino Sugars Biochemistry Cell culture Insect Science DNA Viral biology.protein RNA Viral medicine.drug |
| Zdroj: | Journal of Virology. 77:11933-11940 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.77.22.11933-11940.2003 |
| Popis: | n -( n -Nonyl)-deoxygalactonojirimycin (n,n-DGJ), an alkylated imino sugar, reduces the amount of HBV DNA produced within the stably transfected HBV-producing HepG2.2.15 line in culture and is under consideration for development as a human therapeutic. n,n-DGJ does not appear to inhibit HBV DNA polymerase activity or envelop antigen production (A. Mehta, S. Carrouee, B. Conyers, R. Jordan, T. Butters, R. A. Dwek, and T. M. Block, Hepatology 33:1488-1495, 2001), and the mechanism of antiviral action is unknown. In this study, the step in the virus life cycle affected by n,n-DGJ was explored. Using Northern analysis and immunoprecipitation with anti-HBc antibody, we found that, under conditions in which cell viability was not affected but viral DNA production was substantially reduced, neither the amount of HBV transcription products nor the core polypeptide was detectably reduced. However, the pregenomic RNA, endogenous polymerase activity, and core polypeptide sedimenting in sucrose gradients with a density consistent with that of assembled nucleocapsids were significantly less in the HepG2.2.15 cells incubated with n,n-DGJ. These data suggest that n,n-DGJ either prevents the maturation of HBV nucleocapsids or destabilizes the formed nucleocapsids. Although the cellular and viral mediators of this inhibition are not known, depletion of nucleocapsid has been attributed to some other compounds as well as interferon's mechanism of anti-HBV action. The similarities and differences between this alkylated imino sugar and these other mediators are discussed. |
| Databáze: | OpenAIRE |
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