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Amino acids 1-20 of the hepatitis C virus (HCV) core protein specifically inhibit HCV IRES- dependent translation in Hep G2 cells, and inhibit both HCV IRES- and cap-dependent translation in HuH7 and CV-1 cells.

Li, Dongsheng, Takyar, Seyed Taghi, Lott, William B. and Gowans, Eric J. (2003) Amino acids 1-20 of the hepatitis C virus (HCV) core protein specifically inhibit HCV IRES- dependent translation in Hep G2 cells, and inhibit both HCV IRES- and cap-dependent translation in HuH7 and CV-1 cells.. Journal of General Virology, 84 4: 815-825.

Document type: Journal Article
Collections: School of Medicine Publications   Clinical Medical Virology Centre Publications  

Author(s) Li, Dongsheng
Takyar, Seyed Taghi
Lott, William B.
Gowans, Eric J.
Title Amino acids 1-20 of the hepatitis C virus (HCV) core protein specifically inhibit HCV IRES- dependent translation in Hep G2 cells, and inhibit both HCV IRES- and cap-dependent translation in HuH7 and CV-1 cells.
Journal name Journal of General Virology
Publication date 2003
Volume number 84
Issue number 4
ISSN 0022-1317
Start page 815
End page 825
Total pages 11
Editor(s) G. L. Smith
Place of publication Great Britain
Publisher Society for General Microbiology
Collection year 2003
Language eng
Subject C1
270303 Virology
730101 Infectious diseases
Abstract A self-modulating mechanism by the hepatitis C virus (HCV) core protein has been suggested to influence the level of HCV replication, but current data on this subject are contradictory. We examined the effect of wild-type and mutated core protein on HCV IRES- and cap-dependent translation. The wild-type core protein was shown to inhibit both IRES- and cap-dependent translation in an in vitro system. This effect was duplicated in a dose-dependent manner with a synthetic peptide representing amino acids 1-20 of the HCV core protein. This peptide was able to bind to the HCV IRES as shown by a mobility shift assay. In contrast, a peptide derived from the hepatitis B virus (HBV) core protein that contained a similar proportion of basic residues was unable to inhibit translation or bind the HCV IRES. A recombinant vaccinia-HCV core virus was used to examine the effect of the HCV core protein on HCV IRES-dependent translation in cells and this was compared with the effects of an HBV core-recombinant vaccinia virus. In CV-1 and HuH7 cells, the HCV core protein inhibited translation directed by the IRES elements of HCV, encephalomyocarditis virus and classical swine fever virus as well as cap-dependent translation, whereas in HepG2 cells, only HCV IRES-dependent translation was affected. Thus, the ability of the HCV core protein to selectively inhibit HCV IRES-dependent translation is cell-specific. N-terminal truncated (aa 1-20) HCV core protein that was expressed from a novel recombinant vaccinia virus in cells abrogated the inhibitory phenotype of the core protein in vivo, consistent with the above in vitro data.
Keyword(s) Hepatitis C virus
HCV
amino acids 1-20
IRES-dependent translation
HepG2 cells
HuH7 cells
CV-1 cells
RNA Replication
Virology
Ribosome Entry Site
Hypervariable Region-1
Structural Proteins
 
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