A small yeast RNA blocks hepatitis C virus internal ribosome entry site (HCV IRES)-mediated translation and inhibits replication of a chimeric poliovirus under translational control of the HCV IRES element

Saumitra Das, Michael Ott, Akemi Yamane, Weimin Tsai, Matthias Gromeier, Frederick Lahser, Sanjeev Gupta, Asim Dasgupta

Research output: Contribution to journalArticle

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Abstract

Hepatitis C virus (HCV) infection frequently leads to chronic hepatitis and cirrhosis of the liver and has been linked to development of hepatocellular carcinoma. We previously identified a small yeast RNA (IRNA) capable of specifically inhibiting poliovirus (PV) internal ribosome entry site (IRES)-mediated translation. Here we report that IRNA specifically inhibits HCV IRES-mediated translation both in vivo and in vitro. A number of human hepatoma (Huh-7) cell lines expressing IRNA were prepared and characterized. Constitutive expression of IRNA was not detrimental to cell growth. HCV IRES-mediated cap-independent translation was markedly inhibited in cells constitutively expressing IRNA compared to control hepatoma cells. However, cap-dependent translation was not significantly affected in these cell lines. Additionally, Huh-7 cells constitutively expressing IRNA became refractory to infection by a PV-HCV chimera in which the PV IRES is replaced by the HCV IRES. In contrast, replication of a PV-encephalomyocarditis virus (EMCV) chimera containing the EMCV IRES element was not affected significantly in the IRNA-producing cell line. Finally, the binding of the La autoantigen to the HCV IRES element was specifically and efficiently competed by IRNA. These results provide a basis for development of novel drugs effective against HCV infection.

Original languageEnglish (US)
Pages (from-to)5638-5647
Number of pages10
JournalJournal of Virology
Volume72
Issue number7
StatePublished - Jul 1998

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Enterovirus C
Hepatitis C virus
Poliovirus
ribosomes
Hepacivirus
translation (genetics)
Yeasts
RNA
yeasts
hepatoma
Encephalomyocarditis virus
Hepatocellular Carcinoma
chimerism
cell lines
Virus Diseases
Cell Line
infection
autoantigens
chronic hepatitis
liver cirrhosis

ASJC Scopus subject areas

  • Immunology

Cite this

A small yeast RNA blocks hepatitis C virus internal ribosome entry site (HCV IRES)-mediated translation and inhibits replication of a chimeric poliovirus under translational control of the HCV IRES element. / Das, Saumitra; Ott, Michael; Yamane, Akemi; Tsai, Weimin; Gromeier, Matthias; Lahser, Frederick; Gupta, Sanjeev; Dasgupta, Asim.

In: Journal of Virology, Vol. 72, No. 7, 07.1998, p. 5638-5647.

Research output: Contribution to journalArticle

Das, Saumitra ; Ott, Michael ; Yamane, Akemi ; Tsai, Weimin ; Gromeier, Matthias ; Lahser, Frederick ; Gupta, Sanjeev ; Dasgupta, Asim. / A small yeast RNA blocks hepatitis C virus internal ribosome entry site (HCV IRES)-mediated translation and inhibits replication of a chimeric poliovirus under translational control of the HCV IRES element. In: Journal of Virology. 1998 ; Vol. 72, No. 7. pp. 5638-5647.
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