Diviney, Sinéad, Tuplin, Andrew, Struthers, Madeleine, Armstrong, Victoria, Elliott, Richard M., Simmonds, Peter and Evans, D. J. (David J.). (2008) A hepatitis C virus cis-acting replication element forms a long-range RNA-RNA interaction with upstream RNA sequences in NS5B. Journal of Virology, Vol.82 (No.18). pp. 9008-9022. ISSN 0022-538X

PDF WRAP_Evans_0380313-lf-150211-diviney_et_al_-_final.pdf - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader Download (231Kb)

Abstract

The genome of hepatitis C virus (HCV) contains cis-acting replication elements (CREs) comprised of RNA stem-loop structures located in both the 5' and 3' non-coding regions (NCR), and in the NS5B coding sequence. Through the application of several algorithmically-independent bioinformatic methods to detect phylogenetically-conserved, thermodynamically-favoured RNA secondary structures, we demonstrate a long-range interaction between sequences in the previously described CRE (5BSL3.2, now SL9266) with a previously predicted unpaired sequence located 3' to SL9033, approximately 200 nucleotides upstream. Extensive reverse genetic analysis both supports this prediction and demonstrates a functional requirement in genome replication. By mutagenesis of the Con-1 replicon, we show that disruption of this alternative pairing inhibited replication, a phenotype that could be restored to wild-type levels through the introduction of compensating mutations in the upstream region. Substitution of the CRE with the analogous region of different genotypes of HCV produced replicons with phenotypes consistent with the hypothesis that both local and long-range interactions are critical for a fundamental aspect of genome replication. This report further extends the known interactions of the SL9266 CRE, which has also been shown to form a 'kissing loop' interaction with the 3' NCR (8), and suggests that cooperative long-range binding with both 5' and 3' sequences stabilises the CRE at the core of a complex pseudoknot. Alternatively, if the long-range interactions are mutually exclusive, the SL9266 CRE may function as a molecular switch controlling a critical aspect of HCV genome replication.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Hepatitis C virus -- Genetics
Journal or Publication Title:	Journal of Virology
Publisher:	American Society for Microbiology
ISSN:	0022-538X
Date:	September 2008
Volume:	Vol.82
Number:	No.18
Page Range:	pp. 9008-9022
Identification Number:	10.1128/JVI.02326-07
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Medical Research Council (Great Britain) (MRC), GlaxoSmithKline
References:	1. Blight, K. J., A. A. Kolykhalov, and C. M. Rice. 2000. Efficient initiation of HCV RNA replication in cell culture. Science 290:1972-4. 2. Brierley, I., S. Pennell, and R. J. Gilbert. 2007. Viral RNA pseudoknots: versatile motifs in gene expression and replication. Nat Rev Microbiol 5:598-610. 3. Cheng, J. C., M. F. Chang, and S. C. Chang. 1999. Specific interaction between the hepatitis C virus NS5B RNA polymerase and the 3' end of the viral RNA. J Virol 73:7044-9. 4. Choi, Y. G., and A. L. N. Rao. 2003. Packaging of Brome Mosaic Virus RNA3 Is Mediated through a Bipartite Signal. Journal of Virology 77:9750-9757. 5. Clerte, C., and K. B. Hall. 2006. Characterization of multimeric complexes formed by the human PTB1 protein on RNA. RNA 12:457-475. 6. Ding, Y., C. Y. Chan, and C. E. Lawrence. 2005. RNA secondary structure prediction by centroids in a Boltzmann weighted ensemble. Rna 11:1157-66. 7. Ding, Y., and C. E. Lawrence. 2003. A statistical sampling algorithm for RNA secondary structure prediction. Nucleic Acids Res 31:7280-301. 8. Friebe, P., J. Boudet, J. P. Simorre, and R. Bartenschlager. 2005. Kissing-loop interaction in the 3' end of the hepatitis C virus genome essential for RNA replication. J Virol 79:380-92. 9. Friebe, P., V. Lohmann, N. Krieger, and R. Bartenschlager. 2001. Sequences in the 5' nontranslated region of hepatitis C virus required for RNA replication. J Virol 75:12047-57. 10. Fukushi, S., M. Okada, T. Kageyama, F. B. Hoshino, K. Nagai, and K. Katayama. 2001. Interaction of poly(rC)-binding protein 2 with the 5'-terminal stem loop of the hepatitis C-virus genome. Virus Res 73:67-79. 11. Giege, R. 1996. Interplay of tRNA-like structures from plant viral RNAs with partners of the translation and replication machineries. Proc Natl Acad Sci U S A 93:12078-81. 12. Han, J.-Q., H. L. Townsend, B. K. Jha, J. M. Paranjape, R. H. Silverman, and D. J. Barton. 2007. A Phylogenetically Conserved RNA Structure in the Poliovirus Open Reading Frame Inhibits the Antiviral Endoribonuclease RNase L. J. Virol. 81:5561-5572. 13. Klovins, J., V. Berzins, and J. van Duin. 1998. A long-range interaction in Qbeta RNA that bridges the thousand nucleotides between the M-site and the 3' end is required for replication. Rna 4:948-57. 14. Knudsen, B., and J. Hein. 1999. RNA secondary structure prediction using stochastic context-free grammars and evolutionary history. Bioinformatics 15:446-54. 15. Kuiken, C., C. Combet, J. Bukh, I. T. Shin, G. Deleage, M. Mizokami, R. Richardson, E. Sablon, K. Yusim, J. M. Pawlotsky, and P. Simmonds. 2006. A comprehensive system for consistent numbering of HCV sequences, proteins and epitopes. Hepatology 44:1355-61. 16. Lee, H., H. Shin, E. Wimmer, and A. V. Paul. 2004. cis-acting RNA signals in the NS5B C-terminal coding sequence of the hepatitis C virus genome. J Virol 78:10865-77. 17. Lindenbach, B. D., M. J. Evans, A. J. Syder, B. Wolk, T. L. Tellinghuisen, C. C. Liu, T. Maruyama, R. O. Hynes, D. R. Burton, J. A. McKeating, and C. M. Rice. 2005. Complete replication of hepatitis C virus in cell culture. Science 309:623-6. 18. Lohmann, V., F. Körner, J. Koch, U. Herian, L. Theilmann, and R. Bartenschlager. 1999. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285:110-3. 19. Luo, G., S. Xin, and Z. Cai. 2003. Role of the 5'-proximal stem-loop structure of the 5' untranslated region in replication and translation of hepatitis C virus RNA. J Virol 77:3312-8. 20. Markham, N. R., and M. Zuker. 2005. DINAMelt web server for nucleic acid melting prediction. Nucleic Acids Res 33:W577-81. 21. Matsuda, D., and T. W. Dreher. 2004. The tRNA-like structure of Turnip yellow mosaic virus RNA is a 3'-translational enhancer. Virology 321:36-46. 22. Matsuda, D., S. Yoshinari, and T. W. Dreher. 2004. eEF1A binding to aminoacylated viral RNA represses minus strand synthesis by TYMV RNA-dependent RNA polymerase. Virology 321:47-56. 23. McMullan, L. K., A. Grakoui, M. J. Evans, K. Mihalik, M. Puig, A. D. Branch, S. M. Feinstone, and C. M. Rice. 2007. Evidence for a functional RNA element in the hepatitis C virus core gene. PNAS 104:2879-2884. 24. Pedersen, J. S., I. M. Meyer, R. Forsberg, P. Simmonds, and J. Hein. 2004. A comparative method for predicting and folding RNA secondary structures within protein coding regions. Submitted. 25. Pietschmann, T., A. Kaul, G. Koutsoudakis, A. Shavinskaya, S. Kallis, E. Steinmann, K. Abid, F. Negro, M. Dreux, F. L. Cosset, and R. Bartenschlager. 2006. Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras. Proc Natl Acad Sci U S A 103:7408-13. 26. Reusken, C. B., T. J. Dalebout, P. Eerligh, P. J. Bredenbeek, and W. J. Spaan. 2003. Analysis of hepatitis C virus/classical swine fever virus chimeric 5'NTRs: sequences within the hepatitis C virus IRES are required for viral RNA replication. J Gen Virol 84:1761-9. 27. Rietveld, K., R. van Poelgeest, C. W. A. Pleij, J. H. Van Boom, and L. Bosch. 1982. The tRNA-like structure at the 3' terminus of Turnip Yellow Mosaic Virus RNA. Differences and similarities with canonical tRNA. Nucleic Acids Research 10:1929-1946. 28. Sasaki, J., and K. Taniguchi. 2003. The 5'-End Sequence of the Genome of Aichi Virus, a Picornavirus, Contains an Element Critical for Viral RNA Encapsidation. J. Virol. 77:3542-3548. 29. Simmonds, P., A. Tuplin, and D. J. Evans. 2004. Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: Implications for virus evolution and host persistence. RNA 10:1337-1351. 30. Spangberg, K., and S. Schwartz. 1999. Poly(C)-binding protein interacts with the hepatitis C virus 5' untranslated region. J Gen Virol 80:1371-1376. 31. Tuplin, A., D. J. Evans, and P. Simmonds. 2004. Detailed mapping of RNA secondary structures in core and NS5B-encoding region sequences of hepatitis C virus by RNase cleavage and novel bioinformatic prediction methods. J Gen Virol 85:3037-3047. 32. Tuplin, A., J. Wood, D. J. Evans, A. H. Patel, and P. Simmonds. 2002. Thermodynamic and phylogenetic prediction of RNA secondary structures in the coding region of hepatitis C virus. RNA 8:824-841. 33. Verheije, M. H., R. C. L. Olsthoorn, M. V. Kroese, P. J. M. Rottier, and J. J. M. Meulenberg. 2002. Kissing Interaction between 3' Noncoding and Coding Sequences Is Essential for Porcine Arterivirus RNA Replication. Journal of Virology 76:1521-1526. 34. Wakita, T., T. Pietschmann, T. Kato, T. Date, M. Miyamoto, Z. Zhao, K. Murthy, A. Habermann, H. G. Krausslich, M. Mizokami, R. Bartenschlager, and T. J. Liang. 2005. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11:791-6. 35. Wang, S., and K. A. White. 2007. Riboswitching on RNA virus replication. PNAS 104:10406-10411. 36. You, S., D. D. Stump, A. D. Branch, and C. M. Rice. 2004. A cis-acting replication element in the sequence encoding the NS5B RNA-dependent RNA polymerase is required for hepatitis C virus RNA replication. J Virol 78:1352-66. 37. Yu, L., and L. Markoff. 2005. The Topology of Bulges in the Long Stem of the Flavivirus 3' Stem-Loop Is a Major Determinant of RNA Replication Competence. J. Virol. 79:2309-2324. 38. Zuker, M. 2003. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31:3406-3415.
URI:	http://wrap.warwick.ac.uk/id/eprint/4284

Request changes to a record

Actions (login required)

View Item