Previous Article | Next Article ![]()
J Virol, July 1998, p. 5638-5647, Vol. 72, No. 7
Department of Microbiology and Immunology and
Jonsson Comprehensive Cancer Center, School of Medicine, University of
California, Los Angeles, California 900951;
Department of Medicine, Albert Einstein College of Medicine
of Yeshiva University, Bronx, New York
10461-16022; and
Department of
Molecular Genetics and Microbiology, State University of New York at
Stony Brook, Stony Brook, New York 11794-52223
Received 5 December 1997/Accepted 30 March 1998
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.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, Jonsson Comprehensive Cancer Center,
University of California, 10833 Le Conte Ave., Los Angeles, CA
90095-1747. Phone: (310) 206-8649. Fax: (310) 206-3865. E-mail:
dasgupta{at}ucla.edu.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|