1887

Abstract

A full-length NS3 (NS3F) and a truncated NS3 protein (NS3H) with an RNA helicase domain possess RNA helicase activity. Using an system with a monocistronic reporter RNA or DNA, containing the CSFV 5′-UTR, we observed that both NS3F and NS3H enhanced internal ribosome entry site (IRES)-mediated and cellular translation in a dose-dependent manner, but NS3 protease (NS3P) that lacks a helicase domain did not. NS3F was stronger than NS3H in promoting both translations. These results showed that viral RNA helicase could promote viral and cellular translation, and higher RNA helicase activity might be more efficient. The NS5B protein, the viral replicase, did not significantly affect the IRES-directed or cellular translation alone. NS5B significantly enhanced the stimulative effect of NS3F on both IRES-mediated and cellular translation, but did not affect that of NS3H or NS3P. This suggests that NS5B and NS3 interact via the protease domain during the enhancement of translation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.83341-0
2008-04-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/4/994.html?itemId=/content/journal/jgv/10.1099/vir.0.83341-0&mimeType=html&fmt=ahah

References

  1. Becher P., Thiel H.-J. 2002; Genus Pestivirus ( Flaviviridae ). In The Springer Index of Viruses . pp 327–331Edited by Tidona C. A., Darai G. Heidelberg, Germany: Springer-Verlag;
  2. Bolinger C., Yilmaz A., Hartman T. R., Kovacic M. B., Fernandez S., Ye J., Forget M., Green P. L., Boris-Lawrie K. 2007; RNA helicase A interacts with divergent lymphotropic retroviruses and promotes translation of human T-cell leukemia virus type 1. Nucleic Acids Res 35:2629–2642 [CrossRef]
    [Google Scholar]
  3. Cuthbert J. A. 1994; Hepatitis C: progress and problems. Clin Microbiol Rev 7:505–532
    [Google Scholar]
  4. Fletcher S. P., Jackson R. J. 2002; Pestivirus internal ribosome entry site (IRES) structure and function: elements in the 5′ untranslated region important for IRES function. J Virol 76:5024–5033 [CrossRef]
    [Google Scholar]
  5. Gross T., Siepmann A., Sturm D., Windgassen M., Scarcelli J. J., Seedorf M., Cole C. N., Krebber H. 2007; The DEAD-Box RNA helicase Dbp5 functions in translation termination. Science 315:646–649 [CrossRef]
    [Google Scholar]
  6. Gu B., Liu C., Lin-Goerke J., Maley D. R., Gutshall L. L., Feltenberger C. A., Del Vecchio A. M. 2000; The RNA helicase and nucleotide triphosphatase activities of the bovine viral diarrhea virus NS3 protein are essential for viral replication. J Virol 74:1794–1800 [CrossRef]
    [Google Scholar]
  7. He Y., Yan W., Coito C., Li Y., Gale M., Katze M. G. 2003; The regulation of hepatitis C virus (HCV) internal ribosome-entry site-mediated translation by HCV replicons and nonstructural proteins. J Gen Virol 84:535–543 [CrossRef]
    [Google Scholar]
  8. Heinz F. X., Collett M. S., Purcell R. H., Gould E. A., Howard C. R., Houghton M., Moormann R. J. M., Rice C. M., Thiel H.-J. 2000; Family Flaviviridae . In Virus Taxonomy: Seventh Report of the International Committee on Taxonomy of Viruses pp 859–878Edited by Fauquet C. M., van Regenmortel M. H. V., Bishop D. H. L, Carstens E. B., Estes M. K., Lemon S. M., Maniloff J., Mayo M. A., McGeoch D. J., Pringle C. R., Wickner R. B. San Diego, CA: Academic Press;
    [Google Scholar]
  9. Hellen C. U., Sarnow P. 2001; Internal ribosome entry sites in eukaryotic mRNA molecules. Genes Dev 15:1593–1612 [CrossRef]
    [Google Scholar]
  10. Ishido S., Fujita T., Hotta H. 1998; Complex formation of NS5B with NS3 and NS4A proteins of hepatitis C virus. Biochem Biophys Res Commun 244:35–40 [CrossRef]
    [Google Scholar]
  11. Isken O., Grassmann C. W., Sarisky R. T., Kann M., Zhang S., Grosse F., Kao P. N., Behrens S. E. 2003; Members of the NF90/NFAR protein group are involved in the life cycle of a positive-strand RNA virus. EMBO J 22:5655–5665 [CrossRef]
    [Google Scholar]
  12. Kadare G., Haenni A. L. 1997; Virus-encoded RNA helicases. J Virol 71:2583–2590
    [Google Scholar]
  13. Kalliampakou K. I., Kalamvoki M., Mavromara P. 2005; Hepatitis C virus (HCV) NS5A protein downregulates HCV IRES-dependent translation. J Gen Virol 86:1015–1025 [CrossRef]
    [Google Scholar]
  14. Kato J., Kato N., Yoshida H., Ono-Nita S. K., Shiratori Y., Omata M. 2002; Hepatitis C virus NS4A and NS4B proteins suppress translation in vivo. J Med Virol 66:187–199 [CrossRef]
    [Google Scholar]
  15. Kim D. W., Gwack Y., Han J. H., Choe J. 1995; C-terminal domain of the hepatitis C virus NS3 protein contains an RNA helicase activity. Biochem Biophys Res Commun 215:160–166 [CrossRef]
    [Google Scholar]
  16. Kim Y. K., Lee S. H., Kim C. S., Seol S. K., Jang S. K. 2003; Long-range RNA–RNA interaction between the 5′ nontranslated region and the core coding sequences of hepatitis C virus modulates the IRES-dependent translation. RNA 9:599–606 [CrossRef]
    [Google Scholar]
  17. Kolykhalov A. A., Mihalik K., Feinstone S. M., Rice C. M. 2000; Hepatitis C virus-encoded enzymatic activities and conversed RNA elements in the 3′ nontranslated region are essential for virus replication in vivo. J Virol 74:2046–2051 [CrossRef]
    [Google Scholar]
  18. Li J., Tang H., Mullen T. M., Westberg C., Reddy T. R., Rose D. W., Wong-Staal F. 1999; A role for RNA helicase A in post-transcriptional regulation of HIV type 1. Proc Natl Acad Sci U S A 96:709–714 [CrossRef]
    [Google Scholar]
  19. Luking A., Stahl U., Schmidt U. 1998; The protein family of RNA helicases. Crit Rev Biochem Mol Biol 33:259–296 [CrossRef]
    [Google Scholar]
  20. Meyers G., Thiel H. J. 1995; Cytopathogenicity of classical swine fever virus caused by defective interfering particles. J Virol 69:3683–3689
    [Google Scholar]
  21. Moennig V., Plagemann P. G. W. 1992; The pestiviruses. Adv Virus Res 41:53–98
    [Google Scholar]
  22. Noueiry A. O., Chen J., Ahlquist P. 2000; A mutant allele of essential, general translation initiation factor DED1 selectively inhibits translation of a viral mRNA. Proc Natl Acad Sci U S A 97:12985–12990 [CrossRef]
    [Google Scholar]
  23. Pankraz A., Thiel H. J., Becher P. 2005; Essential and nonessential elements in the 3′ nontranslated region of bovine viral diarrhea virus. J Virol 79:9119–9127 [CrossRef]
    [Google Scholar]
  24. Pause A., Sonenberg N. 1992; Mutational analysis of a DEAD box RNA helicase: the mammalian translation initiation factor eIF-4A. EMBO J 11:2643–2654
    [Google Scholar]
  25. Pfister T., Wimmer E. 1999; Characterization of the nucleoside triphosphatase activity of poliovirus protein 2C reveals a mechanism by which guanidine inhibits poliovirus replication. J Biol Chem 274:6992–7001 [CrossRef]
    [Google Scholar]
  26. Piccininni S., Varaklioti A., Nardelli M., Dave B., Raney K. D., McCarthy J. E. 2002; Modulation of the hepatitis C virus RNA-dependent RNA polymerase activity by the non-structural (NS) 3 helicase and the NS4B membrane protein. J Biol Chem 277:45670–45679 [CrossRef]
    [Google Scholar]
  27. Rozen F., Edery I., Meerovitch K., Dever T. E., Merrick W. C., Sonenberg N. 1990; Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. Mol Cell Biol 10:1134–1144
    [Google Scholar]
  28. Sheng C., Xiao M., Geng X., Liu J., Wang Y., Gu F. 2007; Characterization of interaction of classical swine fever virus NS3 helicase with 3′ untranslated region. Virus Res 129:43–53 [CrossRef]
    [Google Scholar]
  29. Shimoike T., Mimori S., Tani H., Matsuura Y., Miyamura T. 1999; Interaction of hepatitis C virus core protein with viral sense RNA and suppression of its translation. J Virol 73:9718–9725
    [Google Scholar]
  30. Song Y., Friebe P., Tzima E., Junemann C., Bartenschlager R., Niepmann M. 2006; The hepatitis C virus RNA 3′-untranslated region strongly enhances translation directed by the internal ribosome entry site. J Virol 80:11579–11588 [CrossRef]
    [Google Scholar]
  31. Steffens S., Thiel H. J., Behrens S. E. 1999; The RNA-dependent RNA polymerase of different members of the family Flaviviridae exhibits similar properties in vitro . J Gen Virol 80:2583–2590
    [Google Scholar]
  32. Tai C. L., Chi W. K., Chen D. S., Hwang L. H. 1996; The helicase activity associated with hepatitis C virus nonstructural protein 3. J Virol 70:8477–8484
    [Google Scholar]
  33. Warrener P., Collett M. S. 1995; Pestivirus NS3 (p80) protein possesses helicase activity. J Virol 69:1720–1726
    [Google Scholar]
  34. Xiao M., Chen J., Li B. 2003; RNA-dependent RNA polymerase activity of classical swine fever virus NS5B protein expressed in natural host cells. Acta Virol 47:79–85
    [Google Scholar]
  35. Xiao M., Gao J., Wang W., Wang Y., Chen J., Chen J., Li B. 2004; Specific interaction between the classical swine fever virus NS5B protein and the viral genome. Eur J Biochem 271:3888–3896 [CrossRef]
    [Google Scholar]
  36. Xiao M., Li H., Wang Y., Wang X., Wang W., Peng J., Chen J., Li B. 2006; Characterization of the N-terminal domain of classical swine fever virus RNA-dependent RNA polymerase. J Gen Virol 87:347–356 [CrossRef]
    [Google Scholar]
  37. Xu J., Mendez E., Caron P. R., Lin C., Murcko M. A., Collett M. C., Rice C. M. 1997; Bovine viral diarrhea virus: polyprotein cleavage sites, cofactor requirements, and molecular model of an enzyme essential for pestivirus replication. J Virol 71:5312–5322
    [Google Scholar]
  38. Yu H., Grassmann C. W., Behrens S. E. 1999; Sequence and structural elements at the 3′ terminus of bovine viral diarrhea virus genomic RNA: functional role during RNA replication. J Virol 73:3638–3648
    [Google Scholar]
  39. Zhang J., Yamada O., Yoshida H., Iwai T., Araki H. 2002; Autogenous translational inhibition of core protein: implication for switch from translation to RNA replication in hepatitis C virus. Virology 293:141–150 [CrossRef]
    [Google Scholar]
  40. Zhang C., Kim Y. C., Kumar R., Yuan F., Shi P. Y., Kao C., Luo G. 2005; Stimulation of hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase activity by the NS3 protease domain and by HCV RNA-dependent RNA polymerase. J Virol 79:8687–8697 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.83341-0
Loading
/content/journal/jgv/10.1099/vir.0.83341-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error