Abstract | BACKGROUND: METHODS:
eIF3 expression was analyzed by TaqMan polymerase chain reaction, Northern and Western blot analysis of HepG2 cells, and liver biopsies. Functional effects of iron on HCV mRNA translation were estimated by use of transient transfection experiments with bicistronic vectors. RESULTS:
Iron treatment of HepG2 cells increased eIF3 mRNA and protein expression, whereas iron chelation reduced it. Accordingly, iron-dependent stimulation of eIF3 specifically induced the expression of reporter genes under the control of regulatory HCV mRNA stem-loop structures. Moreover, a positive association between liver iron levels, eIF3 expression, and HCV expression was found when liver-biopsy samples from HCV-infected patients were analyzed. CONCLUSION:
Iron promotes the translation of HCV by stimulating the expression of eIF3, which may be one reason for the negative association between liver iron overload and HCV infection. Modulation of the affinity of eIF3 to bind to HCV mRNA may be a promising target for the treatment of chronic HCV infection.
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Authors | Igor Theurl, Heinz Zoller, Peter Obrist, Christian Datz, Felix Bachmann, Richard M Elliott, Guenter Weiss |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 190
Issue 4
Pg. 819-25
(Aug 15 2004)
ISSN: 0022-1899 [Print] United States |
PMID | 15272411
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chlorides
- Eukaryotic Initiation Factor-3
- Ferric Compounds
- RNA, Messenger
- RNA, Viral
- ferric chloride
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Topics |
- Biopsy
- Blotting, Northern
- Blotting, Western
- Cell Line, Tumor
- Chlorides
- Eukaryotic Initiation Factor-3
(metabolism)
- Ferric Compounds
(pharmacology)
- Gene Expression Regulation, Viral
- Genes, Reporter
- Hepacivirus
(genetics, isolation & purification)
- Hepatitis C, Chronic
(drug therapy, metabolism, pathology)
- Homeostasis
- Humans
- Liver
(metabolism, pathology)
- Polymerase Chain Reaction
- Protein Biosynthesis
- RNA, Messenger
(analysis)
- RNA, Viral
(genetics)
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