1887

Abstract

Several RNA interactions are thought to play a role in the regulation of the hepatitis C virus (HCV) life cycle. Most of these interactions involve the 5BSL3.2 domain and therefore occur at the 3′ end of the viral genomic RNA. A long-range interaction has also been described between 5BSL3.2 and the 5′ untranslated region (UTR). Another interaction involves the SLVI stem loop of the core coding region and the 5′UTR. We aimed to analyse the role of this SLVI domain, which likely interferes with others interactions. By evaluating RNA stability, translation and RNA synthesis, we showed that the SLVI stem loop extensively modulates the effect of the interactions mediated by the 5BSL3.2 domain and strongly affects the IIId/5BSL3.2 interaction. Numerous interactions in HCV genomic RNA have been described in the UTRs and the coding sequence but their roles are poorly understood. We showed that the SLVI domain located in the core coding sequence plays an important role in the translation of the polyprotein, but also in the modulation of long-range RNA interactions centred on the 5BSL3.2 domain. The SLVI domain has been absent from most studies, especially from the extensively used subgenomic replicon; our data highlight the importance of this domain in the studies of these long-range interactions in the HCV life cycle.

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2017-04-01
2020-11-24
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References

  1. Poynard T, Yuen M-F, Ratziu V, Lai CL. Viral hepatitis C. The Lancet 2003;362:2095–2100 [CrossRef]
    [Google Scholar]
  2. Thomas DL. Global control of hepatitis C: where challenge meets opportunity. Nat Med 2013;19:850–858 [CrossRef][PubMed]
    [Google Scholar]
  3. Hoofnagle JH. Course and outcome of hepatitis C. Hepatology 2002;36:S21–S29 [CrossRef][PubMed]
    [Google Scholar]
  4. Seeff LB. Natural history of chronic hepatitis C. Hepatology 2002;36:S35–S46 [CrossRef][PubMed]
    [Google Scholar]
  5. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol 2007;13:2436–2441 [CrossRef][PubMed]
    [Google Scholar]
  6. Kim DY, Ahn SH, Han KH. Emerging therapies for hepatitis C. Gut Liver 2014;8:471–479 [CrossRef][PubMed]
    [Google Scholar]
  7. Bartenschlager R, Lohmann V. Replication of hepatitis C virus. J Gen Virol 2000;81:1631–1648 [CrossRef][PubMed]
    [Google Scholar]
  8. Friebe P, Bartenschlager R. Genetic analysis of sequences in the 3′ nontranslated region of hepatitis C virus that are important for RNA replication. J Virol 2002;76:5326–5338 [CrossRef][PubMed]
    [Google Scholar]
  9. Lohmann V, Körner F, Koch J, Herian U, Theilmann L et al. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 1999;285:110–113 [CrossRef][PubMed]
    [Google Scholar]
  10. Thurner C, Witwer C, Hofacker IL, Stadler PF. Conserved RNA secondary structures in Flaviviridae genomes. J Gen Virol 2004;85:1113–1124 [CrossRef][PubMed]
    [Google Scholar]
  11. Schuppli D, Miranda G, Qiu S, Weber H. A branched stem-loop structure in the M-site of bacteriophage Qβ RNA is important for template recognition by Qβ replicase holoenzyme. J Mol Biol 1998;283:585–593 [CrossRef][PubMed]
    [Google Scholar]
  12. Nagashima S, Sasaki J, Taniguchi K. The 5′-terminal region of the Aichi virus genome encodes cis-acting replication elements required for positive- and negative-strand RNA synthesis. J Virol 2005;79:6918–6931 [CrossRef][PubMed]
    [Google Scholar]
  13. Mcknight KL. The human rhinovirus internal cis-acting replication element (cre) exhibits disparate properties among serotypes. Arch Virol 2003;148:2397–2418 [CrossRef][PubMed]
    [Google Scholar]
  14. Goodfellow IG, Kerrigan D, Evans DJ. Structure and function analysis of the poliovirus cis-acting replication element (CRE). RNA 2003;9:124–137 [CrossRef][PubMed]
    [Google Scholar]
  15. Frolov I, Schlesinger S. Translation of Sindbis virus mRNA: effects of sequences downstream of the initiating codon. J Virol 1994;68:8111–8117[PubMed]
    [Google Scholar]
  16. Monkewich S, Lin HX, Fabian MR, Xu W, Na H et al. The p92 polymerase coding region contains an internal RNA element required at an early step in Tombusvirus genome replication. J Virol 2005;79:4848–4858 [CrossRef][PubMed]
    [Google Scholar]
  17. Garlapati S, Chou J, Wang CC. Specific secondary structures in the capsid-coding region of giardiavirus transcript are required for its translation in Giardia lamblia. J Mol Biol 2001;308:623–638 [CrossRef][PubMed]
    [Google Scholar]
  18. Kim YK, Lee SH, Kim CS, Seol SK, Jang SK. 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 2003;9:599–606 [CrossRef][PubMed]
    [Google Scholar]
  19. Friebe P, Boudet J, Simorre JP, Bartenschlager R. Kissing-loop interaction in the 3′ end of the hepatitis C virus genome essential for RNA replication. J Virol 2005;79:380–392 [CrossRef][PubMed]
    [Google Scholar]
  20. Diviney S, Tuplin A, Struthers M, Armstrong V, Elliott RM et al. A hepatitis C virus cis-acting replication element forms a long-range RNA-RNA interaction with upstream RNA sequences in NS5B. J Virol 2008;82:9008–9022 [CrossRef][PubMed]
    [Google Scholar]
  21. Romero-Lopez C, Diaz-Gonzalez R, Barroso-Deljesus A, Berzal-Herranz A. Inhibition of HCV replication and IRES-dependent translation by an RNA molecule. J Gen Virol 2009;90:1659–1669[Crossref]
    [Google Scholar]
  22. Dumas E, Masante C, Astier-Gin T, Lapaillerie D, Ventura M. The hepatitis C virus mini-genome: a new cellular model for studying viral replication. J Virol Methods 2007;142:59–66 [CrossRef][PubMed]
    [Google Scholar]
  23. Masante C, Mahias K, Lourenço S, Dumas E, Cahour A et al. Seven nucleotide changes characteristic of the hepatitis C virus genotype 3 5' untranslated region: correlation with reduced in vitro replication. J Gen Virol 2008;89:212–221 [CrossRef][PubMed]
    [Google Scholar]
  24. Fricke M, Dünnes N, Zayas M, Bartenschlager R, Niepmann M et al. Conserved RNA secondary structures and long-range interactions in hepatitis C viruses. RNA 2015;21:1219–1232 [CrossRef][PubMed]
    [Google Scholar]
  25. Bitard J, Chognard G, Dumas E, Rumi J, Masante C et al. Hijacking hepatitis C viral replication with a non-coding replicative RNA. Antiviral Res 2010;87:9–15 [CrossRef][PubMed]
    [Google Scholar]
  26. Tuplin A, Struthers M, Cook J, Bentley K, Evans DJ. Inhibition of HCV translation by disrupting the structure and interactions of the viral CRE and 3′ X-tail. Nucleic Acids Res 2015;43:2914–2926 [CrossRef][PubMed]
    [Google Scholar]
  27. Wang L, Jeng KS, Lai MM, Poly LMMC. Poly(C)-binding protein 2 interacts with sequences required for viral replication in the hepatitis C virus (HCV) 5' untranslated region and directs HCV RNA replication through circularizing the viral genome. J Virol 2011;85:7954–7964 [CrossRef][PubMed]
    [Google Scholar]
  28. Díaz-Toledano R, Ariza-Mateos A, Birk A, Martínez-García B, Gómez J. In vitro characterization of a miR-122-sensitive double-helical switch element in the 5′ region of hepatitis C virus RNA. Nucleic Acids Res 2009;37:5498–5510 [CrossRef][PubMed]
    [Google Scholar]
  29. Cheng JC, Chang MF, Chang SC. Specific interaction between the hepatitis C virus NS5B RNA polymerase and the 3′ end of the viral RNA. J Virol 1999;73:7044–7049[PubMed]
    [Google Scholar]
  30. Lee JC, Chang CF, Chi YH, Hwang DR, Hsu JT. A reporter-based assay for identifying hepatitis C virus inhibitors based on subgenomic replicon cells. J Virol Methods 2004;116:27–33 [CrossRef][PubMed]
    [Google Scholar]
  31. Kanamori H, Yuhashi K, Ohnishi S, Koike K, Kodama T. RNA-dependent RNA polymerase of hepatitis C virus binds to its coding region RNA stem-loop structure, 5BSL3.2, and its negative strand. J Gen Virol 2010;91:1207–1212 [CrossRef][PubMed]
    [Google Scholar]
  32. Fernández-Sanlés A, Berzal-Herranz B, González-Matamala R, Ríos-Marco P, Romero-López C et al. RNA aptamers as molecular tools to study the functionality of the hepatitis C virus CRE region. Molecules 2015;20:16030–16047 [CrossRef][PubMed]
    [Google Scholar]
  33. Oakland TE, Haselton KJ, Randall G. EWSR1 binds the hepatitis C virus cis-acting replication element and is required for efficient viral replication. J Virol 2013;87:6625–6634 [CrossRef][PubMed]
    [Google Scholar]
  34. Masante C, Jaubert C, Palau W, Plissonneau J, Besnard L et al. Mutations of the SL2 dimerization sequence of the hepatitis C genome abrogate viral replication. Cell Mol Life Sci 2015;72:3375–3385 [CrossRef][PubMed]
    [Google Scholar]
  35. Waxman S, Wurmbach E. De-regulation of common housekeeping genes in hepatocellular carcinoma. BMC Genomics 2007;8:243–252 [CrossRef][PubMed]
    [Google Scholar]
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