Document Detail


Cell cycle regulation of hepatitis C virus internal ribosomal entry site-directed translation.
MedLine Citation:
PMID:  10611164     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Translation of the hepatitis C virus (HCV) polyprotein is mediated by an internal ribosome entry site (IRES) that is located within the 5' nontranslated segment of the viral RNA. This RNA segment is known to form binary complexes with isolated 40S ribosome subunits in vitro, but there is little understanding of how the process of virus translation is regulated in vivo. METHODS: We established 2 stably transformed cell lines from Huh-7 cells that constitutively express dicistronic RNA transcripts containing sequences encoding 2 reporter proteins (Renilla luciferase and firefly luciferase) separated by a functional HCV IRES. The translation of the upstream Renilla luciferase reading frame is initiated in these cells by the usual cellular cap-dependent mechanism, whereas translation of the downstream firefly luciferase reading frame is initiated by the IRES. RESULTS: Compared with cap-dependent translation, the activity of the IRES was greatest in actively growing cells and relatively reduced in resting cells. In synchronized cultures of these stably transformed cells, the IRES activity varied with the cell cycle and was greatest during the mitotic (M) phases and lowest during the quiescent (G(0)) phases. CONCLUSIONS: These findings suggest that HCV translation is regulated by cellular proteins that vary in abundance during the cell cycle and that viral translation may be enhanced by factors that stimulate the regeneration of hepatocytes in patients with chronic hepatitis C.
Authors:
M Honda; S Kaneko; E Matsushita; K Kobayashi; G A Abell; S M Lemon
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Gastroenterology     Volume:  118     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-01-19     Completed Date:  2000-01-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  152-62     Citation Subset:  AIM; IM    
Affiliation:
First Department of Internal Medicine, Kanazawa University, Kanazawa, Japan. mhonda@medf.m.kanazawa-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
5' Untranslated Regions / physiology*
Animals
Beetles / enzymology
Cell Cycle / physiology*
Cell Line, Transformed
Cycloheximide / pharmacology
Genes, Reporter
Hepacivirus / genetics*
Luciferases / metabolism
Protein Biosynthesis*
RNA, Viral / genetics*
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
U19-AI40035/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/5' Untranslated Regions; 0/RNA, Viral; 66-81-9/Cycloheximide; EC 1.13.12.-/Luciferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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