PMID- 14738556
OWN - NLM
STAT- MEDLINE
DCOM- 20040330
LR  - 20191108
IS  - 1352-0504 (Print)
IS  - 1352-0504 (Linking)
VI  - 11
IP  - 1
DP  - 2004 Jan
TI  - Effect of interferon alpha and cell cycle progression on translation mediated by 
      the hepatitis C virus 5' untranslated region: a study using a transgenic mouse 
      model.
PG  - 33-44
AB  - The effect of interferon alpha (IFN alpha) and the progression of the cell cycle 
      on translation mediated by the 5' untranslated region (5'UTR) of hepatitis C 
      virus (HCV) was evaluated in a transgenic mouse model containing the 
      beta-galactosidase (beta-gal) gene under the control of the mouse albumin 
      promoter and HCV 5'UTR. The transgene was exclusively expressed in the liver and 
      specifically in hepatocytes around the periportal area. IFN alpha significantly 
      suppressed the expression of both the beta-gal gene product and its enzymatic 
      activity at 6 h after the treatment of the mice. The mRNA level of the transgene 
      and endogenous albumin gene expression were not affected, so this suppression was 
      considered to be specific to 5'UTR-directed translation. Phosphorylation of the 
      Stat1 protein was observed in the liver extract 20 min after the treatment, thus 
      confirming a specific known effect of IFN alpha in vivo. We suggest that 
      suppression of 5'UTR-directed translation may be one of the mechanisms whereby 
      IFN alpha exerts its anti-viral activity. We further investigated whether the 
      restriction of 5'UTR-directed translation in periportal hepatocytes may be 
      explained by the proliferative state of the cell. Transgene expression was 
      slightly enhanced in the liver 48 h after partial hepatectomy when a substantial 
      number of hepatocytes entered cell cycle progression. However, 5'UTR-directed 
      translation could not be detected in hepatocellular carcinoma lesions in 
      transgenic mice that were induced to develop such tumours. We suggest that the 
      state of differentiation of the cell, and not its proliferative capacity, is 
      important for supporting HCV expression. This animal model may be a useful tool 
      to dissect the control of HCV expression and to search for ways to block viral 
      replication.
FAU - Takeda, Y
AU  - Takeda Y
AD  - The Third Department of Internal Medicine, Niigata University School of Medicine, 
      Niigata, Japan.
FAU - Okoshi, S
AU  - Okoshi S
FAU - Suzuki, K
AU  - Suzuki K
FAU - Yano, M
AU  - Yano M
FAU - Gangemi, J D
AU  - Gangemi JD
FAU - Jay, G
AU  - Jay G
FAU - Asakura, H
AU  - Asakura H
FAU - Aoyagi, Y
AU  - Aoyagi Y
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Antiviral Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interferon Type I)
RN  - 0 (RNA, Viral)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (Serum Albumin)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - Animals
MH  - Antiviral Agents/pharmacology
MH  - Carcinoma, Hepatocellular/virology
MH  - Cell Cycle/*physiology
MH  - DNA-Binding Proteins/metabolism
MH  - Gene Expression/drug effects
MH  - Genes, Reporter
MH  - Hepacivirus/*genetics
MH  - Hepatocytes/*cytology/metabolism/virology
MH  - Interferon Type I/*pharmacology
MH  - Lac Operon
MH  - Liver Neoplasms/virology
MH  - Mice
MH  - Mice, Transgenic
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - *Protein Biosynthesis/drug effects
MH  - RNA, Viral/genetics
MH  - Recombinant Proteins
MH  - STAT1 Transcription Factor
MH  - Serum Albumin/genetics
MH  - Trans-Activators/metabolism
MH  - beta-Galactosidase/genetics
EDAT- 2004/01/24 05:00
MHDA- 2004/03/31 05:00
CRDT- 2004/01/24 05:00
PHST- 2004/01/24 05:00 [pubmed]
PHST- 2004/03/31 05:00 [medline]
PHST- 2004/01/24 05:00 [entrez]
AID - 472 [pii]
AID - 10.1046/j.1365-2893.2003.00472.x [doi]
PST - ppublish
SO  - J Viral Hepat. 2004 Jan;11(1):33-44. doi: 10.1046/j.1365-2893.2003.00472.x.