Journal
VIRUS GENES
Volume 37, Issue 2, Pages 154-160Publisher
SPRINGER
DOI: 10.1007/s11262-008-0250-0
Keywords
hepatitis C virus; internal ribosome entry site; iron; iron-responsive element
Categories
Funding
- Ministry of Science and Technology in Korea [FG07-2-22]
Ask authors/readers for more resources
Although increased liver iron in individuals with chronic hepatitis C virus (HCV) is associated with a poor response to interferon therapy, the underlying molecular mechanisms are poorly understood. In this study, we show that iron enhances the translation initiation mediated by the internal ribosome entry site (IRES) of HCV. We also demonstrate by UV cross-linking analysis that specific cellular proteins bind to HCV 5' untranslated region (5' UTR) in an iron-dependent manner. Notably, p85 and p110 are competed out for their binding to HCV 5' UTR when excess amounts of iron-responsive element (IRE) competitor RNAs are treated. This indicates that at least these two factors are common proteins for binding to HCV 5' UTR and IRE. Our results, taken together, suggest that intracellular iron modulates the iron sensing pathway and HCV IRES-dependent translation by changing the binding affinities of the common cellular factors to IRE and HCV IRES, respectively. As a consequence, the coordinated regulation of gene expression by intracellular iron could provide favorable conditions for HCV proliferation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available