Skip to main content
SpringerLink
Log in

Recombination in the evolution of human rhinovirus genomes

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Human rhinoviruses (HRV) are highly prevalent human respiratory pathogens that belong to the genus Enterovirus. Although recombination within the coding region is frequent in other picornavirus groups, most evidence of recombination in HRV has been restricted to the 5’ untranslated region. We analysed the occurrence of recombination within published complete genome sequences of members of all three HRV species and additionally compared sequences from HRV strains spanning 14 years. HRV-B and HRV-C showed very little evidence of recombination within the coding region. In contrast, HRV-A sequences appeared to have undergone a large number of recombination events, typically involving whole type groups. This suggests that HRV-A may have been subject to extensive recombination during the period of diversification into types. This study demonstrates the rare and sporadic nature of contemporary recombination of HRV strains and contrasts with evidence of extensive recombination within HRV-A and between members of different species during earlier stages in its evolutionary diversification.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Arden KE, McErlean P, Nissen MD, Sloots TP, Mackay IM (2006) Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections. J Med Virol 78:1232–1240

    Article  PubMed  CAS  Google Scholar 

  2. Benschop KS, de Vries M, Minnaar RP, Stanway G, van der Hoek L, Wolthers KC, Simmonds P (2010) Comprehensive full-length sequence analyses of human parechoviruses: diversity and recombination. J Gen Virol 91:145–154

    Article  PubMed  CAS  Google Scholar 

  3. Blomqvist S, Savolainen C, Råman L, Ra L, Roivainen M, Hovi T (2002) Human Rhinovirus 87 and Enterovirus 68 represent a unique serotype with rhinovirus and enterovirus features. J Clin Micro 40:4218–4223

    Article  Google Scholar 

  4. Bochkov YA, Palmenberg AC, Lee W-M, Rathe JA, Amineva SP, Sun X, Pasic TR, Jarjour NN, Liggett SB, Gern JE (2011) Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. Nat Med 17:627–632

    Article  PubMed  CAS  Google Scholar 

  5. Calvert J, Chieochansin T, Benschop KS, McWilliam Leitch EC, Drexler JF, Grywna K, da Costa Ribeiro H, Drosten C, Harvala H, Poovorawan Y, Wolthers KC, Simmonds P (2010) Recombination dynamics of human parechoviruses: investigation of type-specific differences in frequency and epidemiological correlates. J Gen Virol 91:1229–1238

    Article  PubMed  CAS  Google Scholar 

  6. Chidlow GR, Laing IA, Harnett GB, Greenhill AR, Phuanukoonnon S, Siba PM, Pomat WS, Shellam GR, Smith DW, Lehmann D (2012) Respiratory viral pathogens associated with lower respiratory tract disease among young children in the highlands of Papua New Guinea. J Clin Virol 54:235–239

    Article  PubMed  Google Scholar 

  7. Cooney MK, Fox JP, Kenny GE (1982) Antigenic groupings of 90 rhinovirus serotypes. Infect Immun 37:642–647

    PubMed  CAS  Google Scholar 

  8. Drummond AJ, Rambaut A (2007) BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7:214

    Article  PubMed  Google Scholar 

  9. Duffy S, Shackelton LA, Holmes EC (2008) Rates of evolutionary change in viruses: patterns and determinants. Nat Rev Genet 9:267–276

    Article  PubMed  CAS  Google Scholar 

  10. Gibbs MJ, Armstrong JS, Gibbs AJ (2000) Sister-scanning: a Monte Carlo procedure for assessing signals in recombinant sequences. Bioinformatics 16:573–582

    Article  PubMed  CAS  Google Scholar 

  11. Guindon S, Gascuel O (2003) A Simple, Fast, and Accurate Algorithm to Estimate Large Phylogenies by Maximum Likelihood. Syst Biol 52:696–704

    Article  PubMed  Google Scholar 

  12. Hamparian VV, Colonno RJ, Cooney MK, Dick EC, Gwaltney JM, Hughes JH, Jordan WS, Kapikian AZ, Mogabgab WJ, Monto A (1987) A collaborative report: rhinoviruses–extension of the numbering system from 89 to 100. Virology 159:191–192

    Article  PubMed  CAS  Google Scholar 

  13. Han TH, Chung JY, Hwang ES, Koo JW (2009) Detection of human rhinovirus C in children with acute lower respiratory tract infections in South Korea. Arch Virol 154:987–991

    Article  PubMed  CAS  Google Scholar 

  14. Harvala H, McIntyre CL, McLeish NJ, Kondracka J, Palmer J, Molyneaux P, Gunson R, Bennett S, Templeton K, Simmonds P (2012) High detection frequency and viral loads of human rhinovirus species A to C in fecal samples; diagnostic and clinical implications. J Med Virol 84:536–542

    Article  PubMed  CAS  Google Scholar 

  15. Harvala H, Robertson I, McWilliam Leitch EC, Benschop K, Wolthers KC, Templeton K, Simmonds P (2008) Epidemiology and clinical associations of human parechovirus respiratory infections. J Clin Microbiol 46:3446–3453

    Article  PubMed  CAS  Google Scholar 

  16. Hicks AL, Duffy S (2011) Genus-Specific Substitution Rate Variability among Picornaviruses. J Virol 85:7942–7947

    Article  PubMed  CAS  Google Scholar 

  17. Huang T, Wang W, Bessaud M, Ren P, Sheng J, Yan H, Zhang J, Lin X, Wang Y, Delpeyroux F, Deubel V (2009) Evidence of recombination and genetic diversity in human rhinoviruses in children with acute respiratory infection. PLoS One 4:e6355

    Article  PubMed  Google Scholar 

  18. Jenkins GM, Rambaut A, Pybus OG, Holmes EC (2002) Rates of molecular evolution in RNA viruses: a quantitative phylogenetic analysis. J Mol Evol 54:156–165

    Article  PubMed  CAS  Google Scholar 

  19. Kapikian A, Conant R, Hamparian V (1967) Rhinoviruses: a numbering system. Nature 213:761–762

    Article  Google Scholar 

  20. Khetsuriani N, Lu X, Teague WG, Kazerouni N, Anderson LJ, Erdman DD (2008) Novel human rhinoviruses and exacerbation of asthma in children. Emerg Infect Dis 14:1793–1796

    Article  PubMed  Google Scholar 

  21. Kistler A, Avila PC, Rouskin S, Wang D, Ward T, Yagi S, Schnurr D, Ganem D, DeRisi JL, Boushey HA (2007) Pan-viral screening of respiratory tract infections in adults with and without asthma reveals unexpected human coronavirus and human rhinovirus diversity. J Infect Dis 196:817–825

    Article  PubMed  CAS  Google Scholar 

  22. Kistler AL, Webster DR, Rouskin S, Magrini V, Credle JJ, Schnurr DP, Boushey HA, Mardis ER, Li H, DeRisi JL (2007) Genome-wide diversity and selective pressure in the human rhinovirus. Virol J 4:40

    Article  PubMed  Google Scholar 

  23. Kosakovsky Pond SL, Posada D, Gravenor MB, Woelk CH, Frost SDW (2006) Automated phylogenetic detection of recombination using a genetic algorithm. Mol Biol Evol 23:1891–1901

    Article  PubMed  Google Scholar 

  24. Kusel MM, de Klerk NH, Holt PG, Kebadze T, Johnston SL, Sly PD (2006) Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: a birth cohort study. Pediatr Infect Dis J 25:680–686

    Article  PubMed  Google Scholar 

  25. Laine P, Savolainen C, Blomqvist S, Hovi T (2005) Phylogenetic analysis of human rhinovirus capsid protein VP1 and 2A protease coding sequences confirms shared genus-like relationships with human enteroviruses. J Gen Virol 86:697–706

    Article  PubMed  CAS  Google Scholar 

  26. Lamson D, Renwick N, Kapoor V, Liu Z, Palacios G, Ju J, Dean A, St George K, Briese T, Lipkin WI (2006) MassTag polymerase-chain-reaction detection of respiratory pathogens, including a new rhinovirus genotype, that caused influenza-like illness in New York State during 2004–2005. J Infect Dis 194:1398–1402

    Article  PubMed  CAS  Google Scholar 

  27. Ledford RM, Patel NR, Demenczuk TM, Watanyar A, Herbertz T, Collett MS, Pevear DC, Irol JV (2004) VP1 Sequencing of All Human Rhinovirus Serotypes : Insights into Genus Phylogeny and Susceptibility to Antiviral Capsid-Binding Compounds. J Virol 78:3663–3674

    Article  PubMed  CAS  Google Scholar 

  28. Lee WM, Kiesner C, Pappas T, Lee I, Grindle K, Jartti T, Jakiela B, Lemanske RF, Shult PA, Gern JE (2007) A diverse group of previously unrecognized human rhinoviruses are common causes of respiratory illnesses in infants. PLoS One 3:e966

    Article  Google Scholar 

  29. Lewis-Rogers N, Bendall ML, Crandall KA (2009) Phylogenetic relationships and molecular adaptation dynamics of human rhinoviruses. Mol Biol Evol 26:969–981

    Article  PubMed  CAS  Google Scholar 

  30. Lindberg AM, Andersson P, Savolainen C, Mulders MN, Hovi T (2003) Evolution of the genome of Human enterovirus B: incongruence between phylogenies of the VP1 and 3CD regions indicates frequent recombination within the species. J Gen Virol 84:1223–1235

    Article  PubMed  CAS  Google Scholar 

  31. Linsuwanon P, Payungporn S, Samransamruajkit R, Posuwan N, Makkoch J, Theanboonlers A, Poovorawan Y (2009) High prevalence of human rhinovirus C infection in Thai children with acute lower respiratory tract disease. J Infect 59:115–121

    Article  PubMed  Google Scholar 

  32. Linsuwanon P, Payungporn S, Suwannakarn K, Chieochansin T, Theamboonlers A, Poovorawan Y (2011) Complete coding sequence characterization and comparative analysis of the putative novel human rhinovirus (HRV) species C and B. Virol J 8:5

    Article  PubMed  CAS  Google Scholar 

  33. Lukashev AN, Lashkevich VA, Ivanova OE, Koroleva GA, Hinkkanen AE, Ilonen J (2003) Recombination in Circulating Enteroviruses. J Virol 77:10423–10431

    Article  PubMed  CAS  Google Scholar 

  34. Lukashev AN, Lashkevich VA, Ivanova OE, Koroleva GA, Hinkkanen AE, Ilonen J (2005) Recombination in circulating Human enterovirus B: independent evolution of structural and non-structural genome regions. J Gen Virol 86:3281–3290

    Article  PubMed  CAS  Google Scholar 

  35. Martin DP, Posada D, Crandall KA, Williamson C (2005) A modified bootscan algorithm for automated identification of recombinant sequences and recombination breakpoints. AIDS Res Hum Retroviruses 21:98–102

    Article  PubMed  CAS  Google Scholar 

  36. Martin DP, Lemey P, Lott M, Moulton V, Posada D, Lefeuvre P (2010) RDP3: a flexible and fast computer program for analyzing recombination. Bioinformatics 26:2462–2463

    Article  PubMed  CAS  Google Scholar 

  37. Martin D, Rybicki E (2000) RDP: detection of recombination amongst aligned sequences. Bioinformatics 16:562–563

    Article  PubMed  CAS  Google Scholar 

  38. McIntyre CL, McWilliam Leitch EC, Savolainen-Kopra C, Hovi T, Simmonds P (2010) Analysis of genetic diversity and sites of recombination in human rhinovirus species C. J Virol 84:10297–10310

    Article  PubMed  CAS  Google Scholar 

  39. McWilliam Leitch EC, Bendig J, Cabrerizo M, Cardosa J, Hyypiä T, Ivanova OE, Kelly A, Kroes AC, Lukashev A, MacAdam A, McMinn P, Roivainen M, Trallero G, Evans DJ, Simmonds P (2009) Transmission networks and population turnover of echovirus 30. J Virol 83:2109–2118

    Article  PubMed  CAS  Google Scholar 

  40. McWilliam Leitch EC, Cabrerizo M, Cardosa J, Harvala H, Ivanova OE, Koike S, Kroes AC, Lukashev AN, Perera D, Roivainen M, Susi P, Trallero G, Evans DJ, Simmonds P (2012) The association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 71. J Virol 86:2676–2685

    Article  PubMed  CAS  Google Scholar 

  41. McWilliam Leitch EC, Cabrerizo M, Cardosa J, Harvala H, Ivanova OE, Kroes AC, Lukashev A, Muir P, Odoom J, Roivainen M, Susi P, Trallero G, Evans DJ, Simmonds P (2010) Evolutionary dynamics and temporal/geographical correlates of recombination in the human enterovirus echovirus types 9, 11, and 30. J Virol 84:9292–9300

    Article  PubMed  CAS  Google Scholar 

  42. McWilliam Leitch EC, Harvala H, Robertson I, Ubillos I, Templeton K, Simmonds P (2009) Direct identification of human enterovirus serotypes in cerebrospinal fluid by amplification and sequencing of the VP1 region. J Clin Microbiol 44:119–124

    CAS  Google Scholar 

  43. Miller EK, Edwards KM, Weinberg GA, Iwane MK, Griffin MR, Hall CB, Zhu Y, Szilagyi PG, Morin LL, Heil LH, Lu X, Williams JV (2009) A novel group of rhinoviruses is associated with asthma hospitalizations. J Allergy Clin Immunol 123(98–104):e1

    PubMed  Google Scholar 

  44. Oberste MS, Maher K, Pallansch MA (2004) Evidence for frequent recombination within species human enterovirus B based on complete genomic sequences of all thirty-seven serotypes. J Virol 78:855–867

    Article  PubMed  CAS  Google Scholar 

  45. Oberste MS, Peñaranda S, Pallansch MA (2004) RNA recombination plays a major role in genomic change during circulation of coxsackie B viruses. J Virol 78:2948–2955

    Article  PubMed  CAS  Google Scholar 

  46. Oberste MS, Maher K, Kilpatrick DR, Flemister MR, Brown BA, Pallansch MA (1999) Typing of human enteroviruses by partial sequencing of VP1. J Clin Microbiol 37:1288–1293

    PubMed  CAS  Google Scholar 

  47. Padidam M, Sawyer S, Fauquet CM (1999) Possible emergence of new geminiviruses by frequent recombination. Virology 265:218–225

    Article  PubMed  CAS  Google Scholar 

  48. Palmenberg AC, Rathe JA, Liggett SB (2010) Analysis of the complete genome sequences of human rhinovirus. J Allergy Clin Immunol 125:1190–1199

    Article  PubMed  CAS  Google Scholar 

  49. Palmenberg AC, Spiro D, Kuzmickas R, Wang S, Djikeng A, Rathe JA, Fraser-Liggett CM, Liggett SB (2009) Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution. Science 324:55–59

    Article  PubMed  CAS  Google Scholar 

  50. Peltola V, Waris M, Osterback R, Susi P, Ruuskanen O, Hyypiä T (2008) Rhinovirus transmission within families with children: incidence of symptomatic and asymptomatic infections. J Infect Dis 197:382–389

    Article  PubMed  Google Scholar 

  51. Posada D, Crandall KA (2001) Evaluation of methods for detecting recombination from DNA sequences: computer simulations. Proc Natl Acad Sci USA 98:13757–13762

    Article  PubMed  CAS  Google Scholar 

  52. Rathe JA, Liu X, Tallon LJ, Gern JE, Liggett SB (2010) Full-genome sequence and analysis of a novel human rhinovirus strain within a divergent HRV-A clade. Arch Virol 155:83–87

    Article  PubMed  CAS  Google Scholar 

  53. Renwick N, Schweiger B, Kapoor V, Liu Z, Villari J, Bullmann R, Miething R, Briese T, Lipkin WI (2007) A recently identified rhinovirus genotype is associated with severe respiratory-tract infection in children in Germany. J Infect Dis 196:1754–1760

    Article  PubMed  Google Scholar 

  54. Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    PubMed  CAS  Google Scholar 

  55. Santti J, Hyypiä T, Kinnunen L, Salminen M (1999) Evidence of recombination among enteroviruses. J Virol 73:8741–8749

    PubMed  CAS  Google Scholar 

  56. Savolainen C, Blomqvist S, Mulders MN, Hovi T (2002) Genetic clustering of all 102 human rhinovirus prototype strains: serotype 87 is close to human enterovirus 70. J Gen Virol 83:333–340

    PubMed  CAS  Google Scholar 

  57. Savolainen C, Mulders MN, Hovi T (2002) Phylogenetic analysis of rhinovirus isolates collected during successive epidemic seasons. Virus Res 85:41–46

    Article  PubMed  CAS  Google Scholar 

  58. Simmonds P (2012) SSE: a nucleotide and amino acid sequence analysis platform. BMC Res Notes 5:50

    Article  PubMed  CAS  Google Scholar 

  59. Simmonds P, McIntyre C, Savolainen-Kopra C, Tapparel C, Mackay IM, Hovi T (2010) Proposals for the classification of human rhinovirus species C into genotypically assigned types. J Gen Virol 91:2409–2419

    Article  PubMed  CAS  Google Scholar 

  60. Simmonds P, Midgley S (2005) Recombination in the genesis and evolution of hepatitis B virus genotypes. J Virol 79:15467–15476

    Article  PubMed  CAS  Google Scholar 

  61. Simmonds P, Welch J (2006) Frequency and dynamics of recombination within different species of human enteroviruses. J Virol 80:483–493

    Article  PubMed  CAS  Google Scholar 

  62. Smith JM (1992) Analyzing the mosaic structure of genes. J Mol Evol 34:126–129

    PubMed  CAS  Google Scholar 

  63. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739

    Article  PubMed  CAS  Google Scholar 

  64. Tapparel C, Junier T, Gerlach D, Cordey S, Van Belle S, Perrin L, Zdobnov EM, Kaiser L (2007) New complete genome sequences of human rhinoviruses shed light on their phylogeny and genomic features. BMC Genomics 8:224

    Article  PubMed  Google Scholar 

  65. Tapparel C, Junier T, Gerlach D, Van-Belle S, Turin L, Cordey S, Mühlemann K, Regamey N, Aubert J-D, Soccal PM, Eigenmann P, Zdobnov E, Kaiser L (2009) New respiratory enterovirus and recombinant rhinoviruses among circulating picornaviruses. Emerg Infect Dis 15:719–726

    Article  PubMed  CAS  Google Scholar 

  66. Tapparel C, L’Huillier AG, Rougemont AL, Beghetti M, Barazzone-Argiroffo C, Kaiser L (2009) Pneumonia and pericarditis in a child with HRV-C infection: a case report. J Clin Virol 45:157–160

    Article  PubMed  Google Scholar 

  67. Wisdom A, McWilliam Leitch EC, Gaunt E, Harvala H, Simmonds P (2009) Screening respiratory samples for detection of human rhinoviruses (HRVs) and enteroviruses: comprehensive VP4-VP2 typing reveals high incidence and genetic diversity of HRV species C. J Clin Microbiol 47:3958–3967

    Article  PubMed  CAS  Google Scholar 

  68. Wisdom A, Kutkowska AE, McWilliam Leitch EC, Gaunt E, Templeton K, Harvala H, Simmonds P (2009) Genetics, recombination and clinical features of human rhinovirus species C (HRV-C) infections; interactions of HRV-C with other respiratory viruses. PLoS One 4:e8518

    Article  PubMed  Google Scholar 

  69. Xatzipsalti M, Kyrana S, Tsolia M, Psarras S, Bossios A, Laza-Stanca V, Johnston SL, Papadopoulos NG (2005) Rhinovirus viremia in children with respiratory infections. Am J Respir Crit Care Med 172:1037–1040

    Article  PubMed  Google Scholar 

  70. de Almeida MB, Zerbinati RM, Tateno AF, Oliveira CM, Romão RM, Rodrigues JC, Pannuti CS, da Silva Filho LV (2010) Rhinovirus C and respiratory exacerbations in children with cystic fibrosis. Emerg Infect Dis 16:996–999

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Eleanor Gaunt for valuable assistance received in the preliminary stages of this work. The authors are also grateful to Heli Harvala, Kate Templeton, Peter McCullough, Julie White, Mary Notman, Eleanor Leslie and Carol Thomson for providing samples, data and other virus testing results from the respiratory sample archive. Chloe McIntyre’s PhD studentship was funded by the Medical Research Council.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Infection and Immunity Division, Roslin Institute, University of Edinburgh, Edinburgh, EH25 9RG, UK

    Chloe L. McIntyre & Peter Simmonds

  2. National Institute for Health and Welfare (THL), Mannerheimintie 166, FIN-00300, Helsinki, Finland

    Carita Savolainen-Kopra & Tapani Hovi

Authors
  1. Chloe L. McIntyre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carita Savolainen-Kopra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tapani Hovi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Simmonds
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chloe L. McIntyre.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 62 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

McIntyre, C.L., Savolainen-Kopra, C., Hovi, T. et al. Recombination in the evolution of human rhinovirus genomes. Arch Virol 158, 1497–1515 (2013). https://doi.org/10.1007/s00705-013-1634-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-013-1634-6

Keywords

Search

Navigation