Crossref journal-article
American Society for Microbiology
Journal of Virology (235)
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), 5638–5647.

Authors 8
  1. Saumitra Das (first)
  2. Michael Ott (additional)
  3. Akemi Yamane (additional)
  4. Weimin Tsai (additional)
  5. Matthias Gromeier (additional)
  6. Frederick Lahser (additional)
  7. Sanjeev Gupta (additional)
  8. Asim Dasgupta (additional)
References 44 Referenced 34
  1. 10.1128/jvi.69.10.6367-6375.1995
  2. 10.1073/pnas.94.6.2249
  3. 10.1073/pnas.93.20.11115
  4. 10.1128/jvi.71.8.6243-6246.1997
  5. 10.1093/nar/20.19.5041
  6. 10.1073/pnas.89.11.4942
  7. 10.1073/pnas.88.6.2451
  8. 10.1055/s-2007-1007399
  9. 10.1128/jvi.66.1.286-295.1992
  10. 10.1128/jvi.68.11.7200-7211.1994
  11. 10.1128/jvi.70.3.1624-1632.1996
  12. 10.1006/bbrc.1994.1246
  13. 10.1128/jvi.71.2.1662-1666.1997
  14. Gamarnik A. V. Andino R. Two functional complexes formed by KH domain containing proteins with the 5′noncoding region of poliovirus RNA.RNA 3 1997 882 892 / RNA / Two functional complexes formed by KH domain containing proteins with the 5′noncoding region of poliovirus RNA by Gamarnik A. V. (1997)
  15. 10.1073/pnas.93.6.2370
  16. 10.1073/pnas.88.5.1711
  17. 10.1073/pnas.90.16.7642
  18. 10.1002/hep.1840140227
  19. 10.1128/jvi.62.8.2636-2643.1988
  20. Kaminski A. Hunt S. L. Patton J. G. Jackson R. J. Direct evidence that polypyrimidine tract binding protein (PTB) is essential for internal initiation of translation of encephalomyocarditis virus RNA.RNA 1 1995 924 938 / RNA / Direct evidence that polypyrimidine tract binding protein (PTB) is essential for internal initiation of translation of encephalomyocarditis virus RNA by Kaminski A. (1995)
  21. 10.1073/pnas.87.24.9524
  22. Kettinen H. Grace K. Grunert S. Clarke B. Rowlands D. Jackson R. Proceedings of the International Symposium on Viral Hepatitis and Liver Diseases Tokyo Nishioka K. Suzuki H. Mishiro S. Oda T. 1994 125 (10.1007/978-4-431-68255-4_34)
  23. 10.1126/science.277.5325.570
  24. 10.1073/pnas.93.4.1412
  25. 10.1038/353090a0
  26. 10.1128/MCB.16.7.3523
  27. 10.1128/jvi.67.7.3798-3807.1993
  28. 10.1101/gad.6.9.1643
  29. 10.1099/0022-1317-72-11-2697
  30. Parsley T. B. Towner J. S. Blyn L. B. Ehrenfled E. Semler B. L. Poly (rc) binding protein 2 forms a ternary complex with the 5′-terminal sequence of poliovirus RNA and the viral 3CD proteinase.RNA 3 1997 1124 1134 / RNA / Poly (rc) binding protein 2 forms a ternary complex with the 5′-terminal sequence of poliovirus RNA and the viral 3CD proteinase by Parsley T. B. (1997)
  31. 10.1038/334320a0
  32. 10.1038/350434a0
  33. 10.1002/j.1460-2075.1995.tb00289.x
  34. 10.1016/0014-5793(95)00458-L
  35. 10.1073/pnas.87.17.6547
  36. 10.1074/jbc.271.24.14134
  37. 10.1128/jvi.68.3.1544-1550.1994
  38. 10.1002/j.1460-2075.1996.tb01106.x
  39. 10.1128/jvi.65.3.1105-1113.1991
  40. 10.1128/jvi.66.3.1476-1483.1992
  41. 10.1128/jvi.67.6.3338-3344.1993
  42. 10.1021/bi00083a030
  43. 10.1073/pnas.94.16.8738
  44. 10.1006/viro.1995.1204
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)
Funders 0

None

@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} }