Abstract
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.
Bibliography
Das, S., Ott, M., Yamane, A., Tsai, W., Gromeier, M., Lahser, F., Gupta, S., & Dasgupta, A. (1998). 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. Journal of Virology, 72(7), 5638â5647.
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Dates
Type | When |
---|---|
Created | 5 years, 8 months ago (Dec. 31, 2019, 1:15 p.m.) |
Deposited | 3 years, 5 months ago (March 4, 2022, 9:59 p.m.) |
Indexed | 1 year, 1 month ago (July 20, 2024, 8:48 p.m.) |
Issued | 27 years, 2 months ago (July 1, 1998) |
Published | 27 years, 2 months ago (July 1, 1998) |
Published Print | 27 years, 2 months ago (July 1, 1998) |
@article{Das_1998, title={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}, volume={72}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.72.7.5638-5647.1998}, DOI={10.1128/jvi.72.7.5638-5647.1998}, number={7}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Das, Saumitra and Ott, Michael and Yamane, Akemi and Tsai, Weimin and Gromeier, Matthias and Lahser, Frederick and Gupta, Sanjeev and Dasgupta, Asim}, year={1998}, month=jul, pages={5638–5647} }