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Analysis of Sequence Diversity of Human Metapneumovirus Collected from Young Children with Acute Respiratory Tract Infections in South India

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Abstract

Background

Human metapneumovirus (hMPV), which has a global distribution, is an important cause of acute respiratory tract infections, especially in children and immunocompromised patients.

Methods

We investigated the genetic variability of partial nucleoprotein (N) gene sequences of hMPV strains identified among young children in South India. The sequences of the N gene were compared with previously reported sequences available in the GenBank repository.

Results

The results showed that strains are localized in a geographically circumscribed area (topotype). The results also demonstrates that viruses from the same genetic lineage can circulate concurrently within a given location during a given season. The close clustering of the majority of our hMPV isolates indicates that the N gene sequences in the virus population are relatively homogeneous, and suggests temporal rather than geographic variations in the evolutionary pattern. In our study, the majority of the strains belonged to genetic lineage B2 (71.1 %), followed by A2b (18.4 %), A2a (7.9 %), and B1 (2.6 %), demonstrating the presence of 4 of the 5 known genotypes of hMPV. Global alignment of the nucleotide sequences showed that the strains are closely related to sequences from Canada, The Netherlands, and Australasia. Differences at the nucleotide level and the amino acid level were identified. The results provide evidence for the diversity of the N gene of hMPV in samples collected from South India compared with global strains. When investigated for selective pressure, the sequences showed 1 positively selected site and 19 negatively selected sites.

Conclusion

These data should prove useful in further investigations of the evolutionary dynamics of hMPV infection.

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References

  1. Costa LF, Yokosawa J, Mantese OC, et al. Respiratory viruses in children younger than five years old with acute respiratory disease from 2001 to 2004 in Uberlândia, MG, Brazil. Mem Inst Oswaldo Cruz Rio de Janeiro. 2006;101(3):301–6.

    Article  CAS  Google Scholar 

  2. Rudan I, Boschi-Pinto C, Biloglav Z, et al. Epidemiology and etiology of childhood pneumonia. Bull World Health Org. 2008;86(5):408–15.

    Article  PubMed  Google Scholar 

  3. van den Hoogen BG, de Jong JC, Groen J, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med. 2001;7((6):719–24.

    Article  PubMed  CAS  Google Scholar 

  4. Mullins JA, Erdman DD, Weinberg GA, et al. Human metapneumovirus infection among children hospitalized with acute respiratory illness. Emerg Infect Dis. 2004;10(4):700–5.

    Article  PubMed  Google Scholar 

  5. Boivin G, Abed Y, Pelletier G, et al. Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups. J Infect Dis. 2002;1806(9):1330–4.

    Article  Google Scholar 

  6. Stockton J, Stephenson I, Fleming D, et al. Human metapneumovirus as a cause of community-acquired respiratory illness. Emer Infect Dis. 2002;8(9):897–901.

    Article  Google Scholar 

  7. Rao BL, Gandhe SS, Pawar SD, et al. First detection of human metapneumovirus in children with acute respiratory infection in India: a preliminary report. J Clin Microbiol. 2004;42(12):5961–2.

    Article  PubMed  CAS  Google Scholar 

  8. Loo LH, Tan BH, Ng LM, et al. Human metapneumovirus in children, Singapore. Emerg Infect Dis. 2007;13(9):1396–8.

    Article  PubMed  CAS  Google Scholar 

  9. Falsey AR, Erdman D, Anderson LJ, et al. Human metapneumovirus infections in young and elderly adults. J Infect Dis. 2003;187(5):785–90.

    Article  PubMed  Google Scholar 

  10. van den Hoogen BG, van Doornum GJ, Fockens JC, et al. Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients. J Infect Dis. 2003;188(10):1571–7.

    Article  PubMed  Google Scholar 

  11. Johnstone J, Majumdar SR, Fox JD, et al. Viral infection in adults hospitalized with community-acquired pneumonia prevalence, pathogens, and presentation. Chest. 2008;134(6):1141–8.

    Article  PubMed  Google Scholar 

  12. Johnstone J, Majumdar SR, Fox JD, et al. Human metapneumovirus pneumonia in adults: results of a prospective study. Clin Infect Dis. 2008;46(4):571–4.

    Article  PubMed  Google Scholar 

  13. García-García ML, Calvo C, Pozo F, et al. Spectrum of respiratory viruses in children with community-acquired pneumonia. Pediatr Infect Dis J. 2012;31(8):808–13.

    Article  PubMed  Google Scholar 

  14. Ordás J, Boga JA, Alvarez-Argüelles M, et al. Role of metapneumovirus in viral respiratory infections in young children. J Clin Microbiol. 2006;44(8):2739–42.

    Article  PubMed  Google Scholar 

  15. Banerjee S, Bharaj P, Sullender W, et al. Human metapneumovirus infections among children with acute respiratory infections seen in a large referral hospital in India. J Clin Virol. 2007;38(1):70–2.

    Article  PubMed  Google Scholar 

  16. Bharaj P, Sullender WM, Kabra SK, et al. Respiratory viral infections detected by multiplex PCR among pediatric patients with lower respiratory tract infections seen at an urban hospital in Delhi from 2005 to 2007. Virol J. 2009;6:89.

    Article  PubMed  Google Scholar 

  17. van den Hoogen BG, Bestebroer TM, Osterhaus AD, et al. Analysis of the genomic sequence of a human metapneumovirus. Virology. 2002;295:119–32.

    Article  PubMed  Google Scholar 

  18. van den Hoogen BG, Herfst S, Sprong L, et al. Antigenic and genetic variability of human metapneumoviruses. Emerg Infect Dis. 2004;10(4):658–66.

    Article  PubMed  Google Scholar 

  19. Derdowski A, Peters TR, Glover N, et al. Human metapneumovirus nucleoprotein and phosphoprotein interact and provide the minimal requirements for inclusion body formation. J Gen Virol. 2008;89:2698–708.

    Article  PubMed  CAS  Google Scholar 

  20. Narayanan H, Sankar S, Simoes EAF, et al. Molecular detection of human metapneumovirus and human bocavirus on oropharyngeal swabs collected from young children with acute respiratory tract infection from rural and peri-urban communities of India (South). Mol Diag Ther. 2012. doi:10.1007/s40291-013-0030-y.

  21. Tamura K, Peterson D, Peterson N, et al. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol. 2011;28(10):2731–9.

    Article  PubMed  CAS  Google Scholar 

  22. Huck B, Scharf G, Neumann-Haefelin D, et al. Novel human metapneumovirus sublineage. Emerg Infect Dis. 2006;12(1):147–50.

    Article  PubMed  CAS  Google Scholar 

  23. Pond SL, Frost SD, Grossman Z, et al. Adaptation to different human populations by HIV-1 revealed by codon-based analyses. PLoS Comput Biol. 2006;2(6):e62.

    Article  PubMed  Google Scholar 

  24. Bastien N, Ward D, Van Caeseele P, et al. Human metapneumovirus infection in the Canadian population. J Clin Microbiol. 2003;41(10):4642–6.

    Article  PubMed  CAS  Google Scholar 

  25. Côté S, Abed Y, Boivin G. Comparative evaluation of real-time PCR assays for detection of the human metapneumovirus. J Clin Microbiol. 2003;41(8):3631–5.

    Article  PubMed  Google Scholar 

  26. Ludewick HP, Abed Y, van Niekerk N, et al. Human metapneumovirus genetic variability, South Africa. Emerg Infect Dis. 2005;11(7):1074–8.

    PubMed  CAS  Google Scholar 

  27. Hua-wei M, Xi-qiang Y, Xiao-dong Z. Characterization of human metapneumoviruses isolated in Chongqing, China. Chin Med J. 2008;121(22):2254–7.

    Google Scholar 

  28. Zhang C, Du LN, Zhang ZY, et al. Detection and genetic diversity of human metapneumovirus in hospitalized children with acute respiratory infections in southwest China. J Clin Microbiol. 2012;50(8):2714–9.

    Article  PubMed  Google Scholar 

  29. Ishiguro N, Ebihara T, Endo R, et al. High genetic diversity of the attachment (G) protein of human metapneumovirus. J Clin Microbiol. 2004;42(8):3406–14.

    Article  PubMed  CAS  Google Scholar 

  30. Arnott A, Vong S, Sek M, et al. Genetic variability of human metapneumovirus amongst an all ages population in Cambodia between 2007 and 2009. Infect Genet Evol. 2011. doi:10.1016/j.meegid.2011.01.016.

  31. Agrawal AS, Roy T, Ghosh S, et al. Genetic variability of attachment (G) and fusion (F) protein genes of human metapneumovirus strains circulating during 2006–2009 in Kolkata, Eastern India. Virol J. 2011;8:67.

    Google Scholar 

  32. Agapov E, Sumino KC, Gaudreault-Keener M, et al. Genetic variability of human metapneumovirus infection: evidence of a shift in viral genotype without a change in illness. J Infect Dis. 2006;193(3):396–403.

    Article  PubMed  CAS  Google Scholar 

  33. Li J, Ren L, Guo L, et al. Evolutionary dynamics analysis of human metapneumovirus subtype A2: genetic evidence for its dominant epidemic. PLoS One. 2012;7(3):e34544.

    Article  PubMed  CAS  Google Scholar 

  34. Omura T, Iizuka S, Tabara K, et al. Detection of human metapneumovirus genomes during an outbreak of bronchitis and pneumonia in a geriatric care home in Shimane, Japan in Autumn 2009. Jpn J Infect Dis. 2011;64:85–7.

    PubMed  Google Scholar 

  35. Pitoiset C, Darniot M, Huet F, Aho SL, Pothier P, Manoha C. Human metapneumovirus genotypes and severity of disease in young children (n = 100) during a 7-year study in Dijon hospital, France. J Med Virol. 2010;82(10):1782–9.

    Article  PubMed  Google Scholar 

  36. Walsh EE, Peterson DR, Falsey AR. Human metapneumovirus infections in adults: another piece of the puzzle. Arch Intern Med. 2008;168(22):2489–96.

    Article  PubMed  Google Scholar 

  37. Regamey N, Kaiser L, Roiha HL, et al. Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study. Pediatr Infect Dis J. 2008;27(2):100–5.

    PubMed  Google Scholar 

  38. von Linstow ML, Eugen-Olsen J, Koch A, et al. Excretion patterns of human metapneumovirus and respiratory syncytial virus among young children. Eur J Med Res. 2006;11(8):329–35.

    Google Scholar 

  39. Williams JV, Harris PA, Tollefson SJ, et al. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N Engl J Med. 2004;350(5):443–50.

    Article  PubMed  CAS  Google Scholar 

  40. Elena SF, Sanjuán R. Adaptive value of high mutation rates of RNA viruses: separating causes from consequences. J Virol. 2005;79(18):11555–8.

    Article  PubMed  CAS  Google Scholar 

  41. de Graaf M, Osterhaus AD, Fouchier RA, et al. Evolutionary dynamics of human and avian metapneumoviruses. J Gen Virol. 2008;89:2933–42.

    Article  PubMed  Google Scholar 

  42. Ferreira HL, Spilki FR, de Almeida RS, et al. Evolution of the fusion (f), attachment (g), and nucleoprotein (n) genes from the avian metapneumovirus subgroup A. Virus Rev Res. 2011;16(1–2):1–7.

    Google Scholar 

  43. Hughes AL, Hughes MA. Patterns of nucleotide difference in overlapping and non-overlapping reading frames of papillomavirus genomes. Virus Res. 2005;113(2):81–8.

    Article  PubMed  CAS  Google Scholar 

  44. Kuzmin IV, Botvinkin AD, McElhinney LM, et al. Molecular epidemiology of terrestrial rabies in the former Soviet Union. J Wildl Dis. 2004;40(4):617–31.

    PubMed  CAS  Google Scholar 

  45. Xu J, Christman MC, Donis RO, Lu G. Evolutionary dynamics of influenza A nucleoprotein (NP) lineages revealed by large-scale sequence analyses. Infect Genet Evol. 2011;11(8):2125–32.

    Article  PubMed  CAS  Google Scholar 

  46. Lo Presti A, Cammarota R, Apostoli P, et al. Genetic variability and circulation pattern of human metapneumovirus isolated in Italy over five epidemic seasons. New Microbiol. 2011;34(4):337–44.

    PubMed  Google Scholar 

  47. Domingo E. Rapid evolution of viral RNA genomes. J Nutr. 1997;127(5):958S–61S.

    PubMed  CAS  Google Scholar 

  48. Domingo E, Sheldon J, Perales C. Viral quasispecies evolution. Microbiol Mol Biol Rev. 2012;76(2):159–216.

    Article  PubMed  CAS  Google Scholar 

  49. Pybus OG, Rambaut A, Belshaw R, et al. Phylogenetic evidence for deleterious mutation load in RNA viruses and its contribution to viral evolution. Mol Biol Evol. 2007;24(3):845–52.

    Article  PubMed  CAS  Google Scholar 

  50. Loewe L. Negative selection. Nat Educ. 2008;1:1.

    Google Scholar 

  51. Ojosnegros S, Agudo R, Sierra M, et al. Topology of evolving, mutagenized viral populations: quasispecies expansion, compression, and operation of negative selection. BMC Evol Biol. 2008;8:207.

    Article  PubMed  Google Scholar 

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Acknowledgments

This research work was funded by the Indian Council of Medical Research (ICMR, grant no. 5/8/7/15/2009/ECD-I). The authors have no conflicts of interest that are directly relevant to the content of this article.

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Correspondence to Sathish Sankar.

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Narayanan, H., Sankar, S., Simoes, E.A.F. et al. Analysis of Sequence Diversity of Human Metapneumovirus Collected from Young Children with Acute Respiratory Tract Infections in South India. Mol Diagn Ther 17, 247–255 (2013). https://doi.org/10.1007/s40291-013-0032-9

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