Evolution and Emergence of Enteroviruses through Intra- and Inter-species Recombination: Plasticity and Phenotypic Impact of Modular Genetic Exchanges in the 5’ Untranslated Region

English version České info

Recombination shapes viral genomes, including those of the pathogenic circulating vaccine-derived polioviruses (cVDPVs), responsible for poliomyelitis outbreaks. The genomes of cVDPVs consist of sequences from vaccine poliovirus (PV) and other enteroviruses (EVs). We investigated the plasticity of cVDPV genomes and the effects of recombination in the 5’ untranslated region (5’ UTR), which is involved in replication, translation and virulence. We rescued a 5’ UTR-defective recombinant cVDPV genome by cotransfecting cells with 5’ UTR RNAs from human EV species EV-A to -D. Hundreds of recombinants were isolated, revealing striking plasticity in this region, with homologous and nonhomologous recombination sites mostly clustered in three hotspots. Recombination with EV-A and -B affected replication and virulence, whereas recombination with EV-C and -D was either neutral or improved viral fitness. This study illustrates how RNA viruses can acquire mosaic genomes through intra- or inter-species recombination, favoring the emergence of new recombinant strains.

Vyšlo v časopise: Evolution and Emergence of Enteroviruses through Intra- and Inter-species Recombination: Plasticity and Phenotypic Impact of Modular Genetic Exchanges in the 5’ Untranslated Region. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005266
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005266

Souhrn

Zdroje

1. Drake JW, Holland JJ. Mutation rates among RNA viruses. Proc Natl Acad Sci U S A. 1999;96(24):13910–3. Epub 1999/11/26. 10570172; PubMed Central PMCID: PMC24164.

2. Domingo E, Sabo D, Taniguchi T, Weissmann C. Nucleotide sequence heterogeneity of an RNA phage population. Cell. 1978;13(4):735–44. Epub 1978/04/01. 657273.

3. Lauring AS, Andino R. Quasispecies theory and the behavior of RNA viruses. PLoS Pathog. 2010;6(7):e1001005. Epub 2010/07/28. doi: 10.1371/journal.ppat.1001005 20661479; PubMed Central PMCID: PMC2908548.

4. Austermann-Busch S, Becher P. RNA structural elements determine frequency and sites of nonhomologous recombination in an animal plus-strand RNA virus. J Virol. 2012;86(13):7393–402. Epub 2012/04/26. doi: 10.1128/JVI.00864-12 22532677; PubMed Central PMCID: PMC3416315.

5. Gmyl AP, Belousov EV, Maslova SV, Khitrina EV, Chetverin AB, Agol VI. Nonreplicative RNA recombination in poliovirus. J Virol. 1999;73(11):8958–65. Epub 1999/10/09. 10516001; PubMed Central PMCID: PMC112927.

6. Holmblat B, Jegouic S, Muslin C, Blondel B, Joffret ML, Delpeyroux F. Nonhomologous Recombination between Defective Poliovirus and Coxsackievirus Genomes Suggests a New Model of Genetic Plasticity for Picornaviruses. mBio. 2014;5(4). Epub 2014/08/07. doi: 10.1128/mBio.01119-14 25096874.

7. Lowry K, Woodman A, Cook J, Evans DJ. Recombination in enteroviruses is a biphasic replicative process involving the generation of greater-than genome length 'imprecise' intermediates. PLoS Pathog. 2014;10(6):e1004191. Epub 2014/06/20. doi: 10.1371/journal.ppat.1004191 24945141; PubMed Central PMCID: PMC4055744.

8. Scheel TK, Galli A, Li YP, Mikkelsen LS, Gottwein JM, Bukh J. Productive homologous and non-homologous recombination of hepatitis C virus in cell culture. PLoS Pathog. 2013;9(3):e1003228. Epub 2013/04/05. doi: 10.1371/journal.ppat.1003228 23555245; PubMed Central PMCID: PMC3610614.

9. Schibler M, Piuz I, Hao W, Tapparel C. Chimeric rhinoviruses obtained via genetic engineering or artificially induced recombination are viable only if the polyprotein coding sequence derives from the same species. J Virol. 2015;89(8):4470–80. Epub 2015/02/06. doi: 10.1128/JVI.03668-14 25653446.

10. Becher P, Orlich M, Thiel HJ. RNA recombination between persisting pestivirus and a vaccine strain: generation of cytopathogenic virus and induction of lethal disease. J Virol. 2001;75(14):6256–64. Epub 2001/06/20. doi: 10.1128/JVI.75.14.6256–6264.2001 11413291; PubMed Central PMCID: PMC114347.

11. Khatchikian D, Orlich M, Rott R. Increased viral pathogenicity after insertion of a 28S ribosomal RNA sequence into the haemagglutinin gene of an influenza virus. Nature. 1989;340(6229):156–7. Epub 1989/07/13. doi: 10.1038/340156a0 2544809.

12. Jegouic S, Joffret ML, Blanchard C, Riquet FB, Perret C, Pelletier I, et al. Recombination between polioviruses and co-circulating Coxsackie A viruses: role in the emergence of pathogenic vaccine-derived polioviruses. PLoS Pathog. 2009;5(5):e1000412. Epub 2009/05/05. doi: 10.1371/journal.ppat.1000412 19412342; PubMed Central PMCID: PMC2669712.

13. Fernandez-Cuartero B, Burgyan J, Aranda MA, Salanki K, Moriones E, Garcia-Arenal F. Increase in the relative fitness of a plant virus RNA associated with its recombinant nature. Virology. 1994;203(2):373–7. Epub 1994/09/01. doi: 10.1006/viro.1994.1496 8053160.

14. Pilipenko EV, Gmyl AP, Maslova SV, Svitkin YV, Sinyakov AN, Agol VI. Prokaryotic-like cis elements in the cap-independent internal initiation of translation on picornavirus RNA. Cell. 1992;68(1):119–31. Epub 1992/01/10. 1310072.

15. Chevaliez S, Szendroi A, Caro V, Balanant J, Guillot S, Berencsi G, et al. Molecular comparison of echovirus 11 strains circulating in Europe during an epidemic of multisystem hemorrhagic disease of infants indicates that evolution generally occurs by recombination. Virology. 2004;325(1):56–70. Epub 2004/07/03. doi: 10.1016/j.virol.2004.04.026 15231386.

16. Oberste MS, Penaranda S, Maher K, Pallansch MA. Complete genome sequences of all members of the species Human enterovirus A. J Gen Virol. 2004;85(Pt 6):1597–607. Epub 2004/05/29. 15166444.

17. Santti J, Hyypia T, Kinnunen L, Salminen M. Evidence of recombination among enteroviruses. J Virol. 1999;73(10):8741–9. Epub 1999/09/11. 10482628; PubMed Central PMCID: PMC112895.

18. Simmonds P, Welch J. Frequency and dynamics of recombination within different species of human enteroviruses. J Virol. 2006;80(1):483–93. Epub 2005/12/15. doi: 10.1128/JVI.80.1.483–493.2006 16352572; PubMed Central PMCID: PMC1317522.

19. McWilliam Leitch EC, Cabrerizo M, Cardosa J, Harvala H, Ivanova OE, Koike S, et al. The association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 71. J Virol. 2012;86(5):2676–85. Epub 2011/12/30. doi: 10.1128/JVI.06065-11 22205739; PubMed Central PMCID: PMC3302253.

20. Lukashev AN. Role of recombination in evolution of enteroviruses. Rev Med Virol. 2005;15(3):157–67. Epub 2004/12/04. doi: 10.1002/rmv.457 15578739.

21. Joffret ML, Jegouic S, Bessaud M, Balanant J, Tran C, Caro V, et al. Common and diverse features of cocirculating type 2 and 3 recombinant vaccine-derived polioviruses isolated from patients with poliomyelitis and healthy children. J Infect Dis. 2012;205(9):1363–73. Epub 2012/03/30. doi: 10.1093/infdis/jis204 22457288.

22. Jiang P, Faase JA, Toyoda H, Paul A, Wimmer E, Gorbalenya AE. Evidence for emergence of diverse polioviruses from C-cluster coxsackie A viruses and implications for global poliovirus eradication. Proc Natl Acad Sci U S A. 2007;104(22):9457–62. Epub 2007/05/23. doi: 10.1073/pnas.0700451104 17517601; PubMed Central PMCID: PMC1874223.

23. Racaniello VR. Picornaviridae: the viruses and their replication. In: Knipe DM, Howley PM, editors. Fields Virology. 1. 5 ed. Philadelphia: Lippincott Williams and Wilkins; 2007. p. 795–838.

24. Knowles NJ, Hovi T, Hyypia T, King AMQ, Lindberg AM, Pallansch MA, et al. Picornaviridae. In: King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ, editors. Virus Taxonomy: Classification and Nomenclature of Viruses: Ninth Report of the International Committee on Taxonomy of Viruses. San Diego: Elsevier; 2012. p. 855–80.

25. Rowlands DJ, Minor PD. Vaccine Strategies. In: Ehrenfeld E, Domingo E, Roos RP, editors. The Picornaviruses. Washington, DC: ASM Press; 2010. p. 431–47.

26. Kew OM, Sutter RW, de Gourville EM, Dowdle WR, Pallansch MA. Vaccine-derived polioviruses and the endgame strategy for global polio eradication. Annu Rev Microbiol. 2005;59:587–635. Epub 2005/09/13. doi: 10.1146/annurev.micro.58.030603.123625 16153180.

27. Combelas N, Holmblat B, Joffret ML, Colbere-Garapin F, Delpeyroux F. Recombination between poliovirus and coxsackie A viruses of species C: a model of viral genetic plasticity and emergence. Viruses. 2011;3(8):1460–84. Epub 2011/10/14. doi: 10.3390/v3081460 21994791; PubMed Central PMCID: PMC3185806.

28. Minor P. Vaccine-derived poliovirus (VDPV): Impact on poliomyelitis eradication. Vaccine. 2009;27(20):2649–52. Epub 2009/05/12. doi: 10.1016/j.vaccine.2009.02.071 19428874.

29. Rakoto-Andrianarivelo M, Guillot S, Iber J, Balanant J, Blondel B, Riquet F, et al. Co-circulation and evolution of polioviruses and species C enteroviruses in a district of Madagascar. PLoS Pathog. 2007;3(12):e191. Epub 2007/12/19. doi: 10.1371/journal.ppat.0030191 18085822; PubMed Central PMCID: PMC2134956.

30. Dedepsidis E, Kyriakopoulou Z, Pliaka V, Kottaridi C, Bolanaki E, Levidiotou-Stefanou S, et al. Retrospective characterization of a vaccine-derived poliovirus type 1 isolate from sewage in Greece. Appl Environ Microbiol. 2007;73(21):6697–704. Epub 2007/09/11. doi: 10.1128/AEM.00535-07 17827314; PubMed Central PMCID: PMC2074943.

31. Kew O, Morris-Glasgow V, Landaverde M, Burns C, Shaw J, Garib Z, et al. Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus. Science. 2002;296(5566):356–9. Epub 2002/03/16. doi: 10.1126/science.1068284 11896235.

32. Shimizu H, Thorley B, Paladin FJ, Brussen KA, Stambos V, Yuen L, et al. Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001. J Virol. 2004;78(24):13512–21. Epub 2004/11/27. doi: 10.1128/JVI.78.24.13512–13521.2004 15564462; PubMed Central PMCID: PMC533948.

33. Bessaud M, Joffret ML, Holmblat B, Razafindratsimandresy R, Delpeyroux F. Genetic relationship between cocirculating Human enteroviruses species C. PLoS One. 2011;6(9):e24823. Epub 2011/09/21. doi: 10.1371/journal.pone.0024823 21931857; PubMed Central PMCID: PMC3171481.

34. Riquet FB, Blanchard C, Jegouic S, Balanant J, Guillot S, Vibet MA, et al. Impact of exogenous sequences on the characteristics of an epidemic type 2 recombinant vaccine-derived poliovirus. J Virol. 2008;82(17):8927–32. Epub 2008/06/27. doi: 10.1128/JVI.00239-08 18579607; PubMed Central PMCID: PMC2519664.

35. Adu F, Iber J, Bukbuk D, Gumede N, Yang SJ, Jorba J, et al. Isolation of recombinant type 2 vaccine-derived poliovirus (VDPV) from a Nigerian child. Virus Res. 2007;127(1):17–25. Epub 2007/04/24. doi: 10.1016/j.virusres.2007.03.009 17449127.

36. Burns CC, Shaw J, Jorba J, Bukbuk D, Adu F, Gumede N, et al. Multiple independent emergences of type 2 vaccine-derived polioviruses during a large outbreak in northern Nigeria. J Virol. 2013;87(9):4907–22. Epub 2013/02/15. doi: 10.1128/JVI.02954-12 23408630; PubMed Central PMCID: PMC3624331.

37. Rakoto-Andrianarivelo M, Gumede N, Jegouic S, Balanant J, Andriamamonjy SN, Rabemanantsoa S, et al. Reemergence of recombinant vaccine-derived poliovirus outbreak in Madagascar. J Infect Dis. 2008;197(10):1427–35. Epub 2008/04/19. doi: 10.1086/587694 18419577.

38. Yang CF, Naguib T, Yang SJ, Nasr E, Jorba J, Ahmed N, et al. Circulation of endemic type 2 vaccine-derived poliovirus in Egypt from 1983 to 1993. J Virol. 2003;77(15):8366–77. Epub 2003/07/15. 12857906; PubMed Central PMCID: PMC165252.

39. Andino R, Rieckhof GE, Baltimore D. A functional ribonucleoprotein complex forms around the 5' end of poliovirus RNA. Cell. 1990;63(2):369–80. Epub 1990/10/19. 2170027.

40. Barton DJ, O'Donnell BJ, Flanegan JB. 5' cloverleaf in poliovirus RNA is a cis-acting replication element required for negative-strand synthesis. Embo J. 2001;20(6):1439–48. Epub 2001/03/17. doi: 10.1093/emboj/20.6.1439 11250909; PubMed Central PMCID: PMC145522.

41. Rieder E, Xiang W, Paul A, Wimmer E. Analysis of the cloverleaf element in a human rhinovirus type 14/poliovirus chimera: correlation of subdomain D structure, ternary protein complex formation and virus replication. J Gen Virol. 2003;84(Pt 8):2203–16. Epub 2003/07/18. 12867653.

42. Vogt DA, Andino R. An RNA element at the 5'-end of the poliovirus genome functions as a general promoter for RNA synthesis. PLoS Pathog. 2010;6(6):e1000936. Epub 2010/06/10. doi: 10.1371/journal.ppat.1000936 20532207; PubMed Central PMCID: PMC2880563.

43. Sweeney TR, Abaeva IS, Pestova TV, Hellen CU. The mechanism of translation initiation on Type 1 picornavirus IRESs. Embo J. 2014;33(1):76–92. Epub 2013/12/21. doi: 10.1002/embj.201386124 24357634; PubMed Central PMCID: PMC3990684.

44. Nicholson R, Pelletier J, Le SY, Sonenberg N. Structural and functional analysis of the ribosome landing pad of poliovirus type 2: in vivo translation studies. J Virol. 1991;65(11):5886–94. Epub 1991/11/01. 1656077; PubMed Central PMCID: PMC250251.

45. Wimmer E, Paul AV. The making of a Picornavirus genome. In: Ehrenfeld E, Domingo E, Roos RP, editors. The Picornaviruses. Washington, DC: ASM Press; 2010. p. 33–55.

46. Kuge S, Nomoto A. Construction of viable deletion and insertion mutants of the Sabin strain of type 1 poliovirus: function of the 5' noncoding sequence in viral replication. J Virol. 1987;61(5):1478–87. Epub 1987/05/01. 3033275; PubMed Central PMCID: PMC254126.

47. Gmyl AP, Pilipenko EV, Maslova SV, Belov GA, Agol VI. Functional and genetic plasticities of the poliovirus genome: quasi-infectious RNAs modified in the 5'-untranslated region yield a variety of pseudorevertants. J Virol. 1993;67(10):6309–16. Epub 1993/10/01. 8396686; PubMed Central PMCID: PMC238059.

48. Bradrick SS, Lieben EA, Carden BM, Romero JR. A predicted secondary structural domain within the internal ribosome entry site of echovirus 12 mediates a cell-type-specific block to viral replication. J Virol. 2001;75(14):6472–81. Epub 2001/06/20. doi: 10.1128/JVI.75.14.6472–6481.2001 11413314; PubMed Central PMCID: PMC114370.

49. Gromeier M, Alexander L, Wimmer E. Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants. Proc Natl Acad Sci U S A. 1996;93(6):2370–5. Epub 1996/03/19. 8637880; PubMed Central PMCID: PMC39803.

50. Johnson VH, Semler BL. Defined recombinants of poliovirus and coxsackievirus: sequence-specific deletions and functional substitutions in the 5'-noncoding regions of viral RNAs. Virology. 1988;162(1):47–57. Epub 1988/01/01. 2827387.

51. Rohll JB, Percy N, Ley R, Evans DJ, Almond JW, Barclay WS. The 5'-untranslated regions of picornavirus RNAs contain independent functional domains essential for RNA replication and translation. J Virol. 1994;68(7):4384–91. Epub 1994/07/01. 8207812; PubMed Central PMCID: PMC236362.

52. Zell R, Klingel K, Sauter M, Fortmuller U, Kandolf R. Coxsackieviral proteins functionally recognize the polioviral cloverleaf structure of the 5'-NTR of a chimeric enterovirus RNA: influence of species-specific host cell factors on virus growth. Virus Res. 1995;39(2–3):87–103. Epub 1995/12/01. 8837877.

53. Harvala H, Kalimo H, Dahllund L, Santti J, Hughes P, Hyypia T, et al. Mapping of tissue tropism determinants in coxsackievirus genomes. J Gen Virol. 2002;83(Pt 7):1697–706. Epub 2002/06/21. 12075089.

54. Gromeier M, Bossert B, Arita M, Nomoto A, Wimmer E. Dual stem loops within the poliovirus internal ribosomal entry site control neurovirulence. J Virol. 1999;73(2):958–64. Epub 1999/01/09. 9882296; PubMed Central PMCID: PMC103915.

55. Jahan N, Wimmer E, Mueller S. A host-specific, temperature-sensitive translation defect determines the attenuation phenotype of a human rhinovirus/poliovirus chimera, PV1(RIPO). J Virol. 2011;85(14):7225–35. Epub 2011/05/13. doi: 10.1128/JVI.01804-09 21561914; PubMed Central PMCID: PMC3126568.

56. Chapman NM, Ragland A, Leser JS, Hofling K, Willian S, Semler BL, et al. A group B coxsackievirus/poliovirus 5' nontranslated region chimera can act as an attenuated vaccine strain in mice. J Virol. 2000;74(9):4047–56. Epub 2001/02/07. 10756016; PubMed Central PMCID: PMC111918.

57. Evans DM, Dunn G, Minor PD, Schild GC, Cann AJ, Stanway G, et al. Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. Nature. 1985;314(6011):548–50. Epub 1985/04/11. 2986004.

58. Kawamura N, Kohara M, Abe S, Komatsu T, Tago K, Arita M, et al. Determinants in the 5' noncoding region of poliovirus Sabin 1 RNA that influence the attenuation phenotype. J Virol. 1989;63(3):1302–9. Epub 1989/03/01. 2536835; PubMed Central PMCID: PMC247827.

59. Macadam AJ, Pollard SR, Ferguson G, Dunn G, Skuce R, Almond JW, et al. The 5' noncoding region of the type 2 poliovirus vaccine strain contains determinants of attenuation and temperature sensitivity. Virology. 1991;181(2):451–8. Epub 1991/04/01. 1707566.

60. Kirkegaard K, Baltimore D. The mechanism of RNA recombination in poliovirus. Cell. 1986;47(3):433–43. Epub 1986/11/07. 3021340.

61. Gallei A, Pankraz A, Thiel HJ, Becher P. RNA recombination in vivo in the absence of viral replication. J Virol. 2004;78(12):6271–81. Epub 2004/05/28. doi: 10.1128/JVI.78.12.6271–6281.2004 15163720; PubMed Central PMCID: PMC416528.

62. Raju R, Subramaniam SV, Hajjou M. Genesis of Sindbis virus by in vivo recombination of nonreplicative RNA precursors. J Virol. 1995;69(12):7391–401. Epub 1995/12/01. 7494243; PubMed Central PMCID: PMC189675.

63. Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 2003;31(13):3406–15. Epub 2003/06/26. 12824337; PubMed Central PMCID: PMC169194.

64. Rousset D, Rakoto-Andrianarivelo M, Razafindratsimandresy R, Randriamanalina B, Guillot S, Balanant J, et al. Recombinant vaccine-derived poliovirus in Madagascar. Emerg Infect Dis. 2003;9(7):885–7. Epub 2003/08/06. doi: 10.3201/eid0907.020692 12899139; PubMed Central PMCID: PMC3023450.

65. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30(12):2725–9. Epub 2013/10/18. doi: 10.1093/molbev/mst197 24132122; PubMed Central PMCID: PMC3840312.

66. Pipkin PA, Wood DJ, Racaniello VR, Minor PD. Characterisation of L cells expressing the human poliovirus receptor for the specific detection of polioviruses in vitro. J Virol Methods. 1993;41(3):333–40. Epub 1993/03/01. 8386181.

67. Koike S, Taya C, Aoki J, Matsuda Y, Ise I, Takeda H, et al. Characterization of three different transgenic mouse lines that carry human poliovirus receptor gene—influence of the transgene expression on pathogenesis. Arch Virol. 1994;139(3–4):351–63. Epub 1994/01/01. 7832641.

68. Nagata N, Iwasaki T, Ami Y, Sato Y, Hatano I, Harashima A, et al. A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21. Virology. 2004;321(1):87–100. Epub 2004/03/23. doi: 10.1016/j.virol.2003.12.008 15033568.

69. Dobrikova E, Florez P, Bradrick S, Gromeier M. Activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3' nontranslated region. Proc Natl Acad Sci U S A. 2003;100(25):15125–30. Epub 2003/12/03. doi: 10.1073/pnas.2436464100 14645707; PubMed Central PMCID: PMC299919.

70. Florez de Sessions P, Dobrikova E, Gromeier M. Genetic adaptation to untranslated region-mediated enterovirus growth deficits by mutations in the nonstructural proteins 3AB and 3CD. J Virol. 2007;81(16):8396–405. Epub 2007/06/01. doi: 10.1128/JVI.00321-07 17537861; PubMed Central PMCID: PMC1951365.

71. Rowe A, Ferguson GL, Minor PD, Macadam AJ. Coding changes in the poliovirus protease 2A compensate for 5'NCR domain V disruptions in a cell-specific manner. Virology. 2000;269(2):284–93. Epub 2001/02/07. doi: 10.1006/viro.2000.0244 10753707.

72. Alexander L, Lu HH, Wimmer E. Polioviruses containing picornavirus type 1 and/or type 2 internal ribosomal entry site elements: genetic hybrids and the expression of a foreign gene. Proc Natl Acad Sci U S A. 1994;91(4):1406–10. Epub 1994/02/15. 7509072; PubMed Central PMCID: PMC43167.

73. Xiang W, Harris KS, Alexander L, Wimmer E. Interaction between the 5'-terminal cloverleaf and 3AB/3CDpro of poliovirus is essential for RNA replication. J Virol. 1995;69(6):3658–67. Epub 1995/06/01. 7745714; PubMed Central PMCID: PMC189081.

74. Simoes EA, Sarnow P. An RNA hairpin at the extreme 5' end of the poliovirus RNA genome modulates viral translation in human cells. J Virol. 1991;65(2):913–21. Epub 1991/02/01. 1846205; PubMed Central PMCID: PMC239832.

75. Borman AM, Deliat FG, Kean KM. Sequences within the poliovirus internal ribosome entry segment control viral RNA synthesis. Embo J. 1994;13(13):3149–57. Epub 1994/07/01. 8039507; PubMed Central PMCID: PMC395206.

76. Ishii T, Shiroki K, Iwai A, Nomoto A. Identification of a new element for RNA replication within the internal ribosome entry site of poliovirus RNA. J Gen Virol. 1999;80 (Pt 4):917–20. Epub 1999/04/22. 10211960.

77. Murray KE, Steil BP, Roberts AW, Barton DJ. Replication of poliovirus RNA with complete internal ribosome entry site deletions. J Virol. 2004;78(3):1393–402. Epub 2004/01/15. 14722294; PubMed Central PMCID: PMC321374.

78. Haller AA, Nguyen JH, Semler BL. Minimum internal ribosome entry site required for poliovirus infectivity. J Virol. 1993;67(12):7461–71. Epub 1993/12/01. 8230467; PubMed Central PMCID: PMC238212.

79. Martinez-Salas E. The impact of RNA structure on picornavirus IRES activity. Trends Microbiol. 2008;16(5):230–7. Epub 2008/04/19. doi: 10.1016/j.tim.2008.01.013 18420413.

80. Le SY, Zuker M. Common structures of the 5' non-coding RNA in enteroviruses and rhinoviruses. Thermodynamical stability and statistical significance. J Mol Biol. 1990;216(3):729–41. Epub 1990/12/05. doi: 10.1016/0022-2836(90)90395-3 2175364.

81. Bailey JM, Tapprich WE. Structure of the 5' nontranslated region of the coxsackievirus b3 genome: Chemical modification and comparative sequence analysis. J Virol. 2007;81(2):650–68. Epub 2006/11/03. doi: 10.1128/JVI.01327-06 17079314; PubMed Central PMCID: PMC1797431.

82. Liu Z, Carthy CM, Cheung P, Bohunek L, Wilson JE, McManus BM, et al. Structural and functional analysis of the 5' untranslated region of coxsackievirus B3 RNA: In vivo translational and infectivity studies of full-length mutants. Virology. 1999;265(2):206–17. Epub 1999/12/22. doi: 10.1006/viro.1999.0048 10600593.

83. Skinner MA, Racaniello VR, Dunn G, Cooper J, Minor PD, Almond JW. New model for the secondary structure of the 5' non-coding RNA of poliovirus is supported by biochemical and genetic data that also show that RNA secondary structure is important in neurovirulence. J Mol Biol. 1989;207(2):379–92. Epub 1989/05/20. 2547075.

84. Nagy PD, Bujarski JJ. Engineering of homologous recombination hotspots with AU-rich sequences in brome mosaic virus. J Virol. 1997;71(5):3799–810. Epub 1997/05/01. 9094655; PubMed Central PMCID: PMC191530.

85. Shapka N, Nagy PD. The AU-rich RNA recombination hot spot sequence of Brome mosaic virus is functional in tombusviruses: implications for the mechanism of RNA recombination. J Virol. 2004;78(5):2288–300. Epub 2004/02/14. 14963125; PubMed Central PMCID: PMC369227.

86. Huang T, Wang W, Bessaud M, Ren P, Sheng J, Yan H, et al. Evidence of recombination and genetic diversity in human rhinoviruses in children with acute respiratory infection. PLoS One. 2009;4(7):e6355. Epub 2009/07/28. doi: 10.1371/journal.pone.0006355 19633719; PubMed Central PMCID: PMC2712091.

87. King AM. Preferred sites of recombination in poliovirus RNA: an analysis of 40 intertypic cross-over sequences. Nucleic Acids Res. 1988;16(24):11705–23. Epub 1988/12/23. 2463516; PubMed Central PMCID: PMC339105.

88. McIntyre CL, McWilliam Leitch EC, Savolainen-Kopra C, Hovi T, Simmonds P. Analysis of genetic diversity and sites of recombination in human rhinovirus species C. J Virol. 2010;84(19):10297–310. Epub 2010/07/30. doi: 10.1128/JVI.00962-10 20668080; PubMed Central PMCID: PMC2937769.

89. Simmonds P. Recombination and selection in the evolution of picornaviruses and other Mammalian positive-stranded RNA viruses. J Virol. 2006;80(22):11124–40. Epub 2006/09/08. doi: 10.1128/JVI.01076-06 16956935; PubMed Central PMCID: PMC1642140.

90. Galli A, Bukh J. Comparative analysis of the molecular mechanisms of recombination in hepatitis C virus. Trends Microbiol. 2014;22(6):354–64. Epub 2014/03/19. doi: 10.1016/j.tim.2014.02.005 24636243.

91. Nagy PD, Bujarski JJ. Efficient system of homologous RNA recombination in brome mosaic virus: sequence and structure requirements and accuracy of crossovers. J Virol. 1995;69(1):131–40. Epub 1995/01/01. 7983703; PubMed Central PMCID: PMC188556.

92. Gallei A, Orlich M, Thiel HJ, Becher P. Noncytopathogenic pestivirus strains generated by nonhomologous RNA recombination: alterations in the NS4A/NS4B coding region. J Virol. 2005;79(22):14261–70. Epub 2005/10/29. doi: 10.1128/JVI.79.22.14261–14270.2005 16254361; PubMed Central PMCID: PMC1280241.

93. White KA, Morris TJ. RNA determinants of junction site selection in RNA virus recombinants and defective interfering RNAs. RNA. 1995;1(10):1029–40. Epub 1995/12/01. 8595558; PubMed Central PMCID: PMC1369329.

94. An W, Telesnitsky A. Effects of varying sequence similarity on the frequency of repeat deletion during reverse transcription of a human immunodeficiency virus type 1 vector. J Virol. 2002;76(15):7897–902. Epub 2002/07/05. 12097604; PubMed Central PMCID: PMC136404.

95. Lin CC, Yang ZW, Iang SB, Chao M. Reduced genetic distance and high replication levels increase the RNA recombination rate of hepatitis delta virus. Virus Res. 2015;195:79–85. Epub 2014/08/31. doi: 10.1016/j.virusres.2014.08.011 25172581.

96. Teoule F, Brisac C, Pelletier I, Vidalain PO, Jegouic S, Mirabelli C, et al. The Golgi protein ACBD3, an interactor for poliovirus protein 3A, modulates poliovirus replication. J Virol. 2013;87(20):11031–46. Epub 2013/08/09. doi: 10.1128/JVI.00304-13 23926333; PubMed Central PMCID: PMC3807280.

97. Sadeuh-Mba SA, Bessaud M, Massenet D, Joffret ML, Endegue MC, Njouom R, et al. High frequency and diversity of species C enteroviruses in Cameroon and neighboring countries. J Clin Microbiol. 2013;51(3):759–70. Epub 2012/12/21. doi: 10.1128/JCM.02119-12 23254123; PubMed Central PMCID: PMC3592076.

98. Reed LJ, Muench M. A simple method for estimating fifty percent endpoints. Am J Hyg. 1938;27:493–7.

99. Bessaud M, Delpeyroux F. Development of a simple and rapid protocol for the production of customized intertypic recombinant polioviruses. J Virol Methods. 2012;186(1–2):104–8. Epub 2012/09/04. doi: 10.1016/j.jviromet.2012.08.001 22939977.

100. Guillot S, Caro V, Cuervo N, Korotkova E, Combiescu M, Persu A, et al. Natural genetic exchanges between vaccine and wild poliovirus strains in humans. J Virol. 2000;74(18):8434–43. Epub 2000/08/23. 10954543; PubMed Central PMCID: PMC116354.

101. Bessaud M, Jegouic S, Joffret ML, Barge C, Balanant J, Gouandjika-Vasilache I, et al. Characterization of the genome of human enteroviruses: design of generic primers for amplification and sequencing of different regions of the viral genome. J Virol Methods. 2008;149(2):277–84. Epub 2008/03/11. doi: 10.1016/j.jviromet.2008.01.027 18329732.