Archives of Virology

, Volume 164, Issue 3, pp 717–724 | Cite as

Analysis of natural recombination and host-related evolutionary dynamics of avian avulavirus 1 isolates based on positive and negative selection from 1948 to 2017

  • Majid EsmaelizadEmail author
  • Vafa Mayahi
Original Article


Adaptation and evolution of avian avulavirus 1, or Newcastle disease virus (NDV), has led to tremendous economic losses worldwide. The occurrence of natural recombination and selection pressure has been traced for NDV based on a few recent reports, but a dominant pattern based on genomic characteristics is lacking. Here, we used bioinformatics tools to search for evidence of recombination in all of the available complete genome sequence of NDV (462 sequences) using RDP4 software. Geographical linkage and host cell relationships of recombinant viruses were also investigated, and a study of the adaptive evolution of avian avulavirus 1 was performed. The results revealed that recombination events could occur in any gene fragment of the NDV genome. Moreover, class I NDV isolates from wild birds could associate to generate a putative recombinant virus with a class II genome backbone. In addition, not only avirulent-virulent hybrid genotypes but also virulent-virulent natural recombinant NDV viruses were generated. Investigation of geographic relationships of recombinant isolates indicated that the highest rate of recombination occurs in Asia and the Middle East, which can be influenced by vaccination failure, evasion of the immune response, live-bird markets, and the bird trade. The M and NP genes were found to have higher negative selection rates than the other genes, which might lead to the deletion of inadaptable sequences and result in more conserved sequences. Based on our analysis, the highest rate of positive selection was observed in the L, F and HN genes, which we suggest could lead to the occurrence of evolved viruses with high pathogenicity and a better chance of survival under extreme conditions.



This study was supported by Grant no. 2-18-18-94129 from the Razi Vaccine and Serum Research Institute.

Compliance with ethical standards

Conflict of interest

The authors declare no competing interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Gould AR, Kattenbelt JA, Selleck P, Hansson E, Della-Porta A, Westbury HA (2001) Virulent Newcastle disease in Australia: molecular epidemiological analysis of viruses isolated prior to and during the outbreaks of 998–2000. Virus Res 77:51–60CrossRefGoogle Scholar
  2. 2.
    Domingo E, Holland JJ (1997) RNA virus mutations for fitness and survival. Annu Rev Microbiol 51:151–178. CrossRefGoogle Scholar
  3. 3.
    Lai MMC (1992) RNA recombination in animal and plant viruses. Microbiol Rev 56:61–79Google Scholar
  4. 4.
    Worobey M, Holmes EC (1999) Evolutionary aspects of recombination in RNA viruses. J Gen Virol 80:2535–2543. CrossRefGoogle Scholar
  5. 5.
    Archer AM, Rico-Hesse R (2002) High genetic divergence and recombination in arenaviruses from the Americas. Virology 304:274–281. CrossRefGoogle Scholar
  6. 6.
    Chare ER, Gould EA, Holmes EC (2003) Phylogenetic analysis reveals a low rate of homologous recombination in negative-sense RNA viruses. J Gen Virol 84:2691–2703. CrossRefGoogle Scholar
  7. 7.
    Gibbs MJ, Armstrong JS, Gibbs AJ (2001) Recombination in the hemagglutinin gene of the 1918 “Spanish flu”. Science 293:1842–1845. CrossRefGoogle Scholar
  8. 8.
    Han GZ, He CQ, Ding NZ, Ma LY (2008) Identification of a natural multirecombinant of Newcastle disease virus. Virology 371:54–60. CrossRefGoogle Scholar
  9. 9.
    Han GZ, Liu XP, Li SS (2008) Cross-species recombination in the haemagglutinin gene of canine distemper virus. Virus Res 136:198–201. CrossRefGoogle Scholar
  10. 10.
    Han GZ, Worobey M (2011) Homologous recombination in negative sense RNA viruses. Viruses 3:1358–1373. CrossRefGoogle Scholar
  11. 11.
    He CQ, Han GZ, Wang D, Liu W, Li GR, Liu XP, Ding NZ (2008) Homologous recombination evidence in human and swine influenza A viruses. Virology 380:12–20. CrossRefGoogle Scholar
  12. 12.
    He CQ, Xie ZX, Han GZ, Dong JB, Wang D, Liu JB, Ma LY, Tang XF, Liu XP, Pang YS, Li GR (2009) Homologous recombination as an evolutionary force in the avian influenza A virus. Mol Biol Evol 26:177–187. CrossRefGoogle Scholar
  13. 13.
    Lukashev AN (2005) Evidence for recombination in Crimean–Congo hemorrhagic fever virus. J Gen Virol 86:2333–2338. CrossRefGoogle Scholar
  14. 14.
    Sironen T, Vaheri A, Plyusnin A (2001) Molecular evolution of Puumala hantavirus. J Virol 75:11803–11810. CrossRefGoogle Scholar
  15. 15.
    Spann KM, Collins PL, Teng MN (2003) Genetic recombination during coinfection of two mutants of human respiratory syncytial virus. J Virol 77:11201–11211. CrossRefGoogle Scholar
  16. 16.
    Wittmann TJ, Biek R, Hassanin A, Rouquet P, Reed P, Yaba P, Pourrut X, Real LA, Gonzalez JP, Leroy EM (2007) Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants. PNAS 104:17123–17127. CrossRefGoogle Scholar
  17. 17.
    Zhang R, Wang X, Su J, Zhao J, Zhang G (2010) Isolation and analysis of two naturally-occurring multi-recombination Newcastle disease viruses in China. Virus Res 151:45–53. CrossRefGoogle Scholar
  18. 18.
    Courtney SC, Gomez D, Susta L, Hines N, Pedersen JC, Miller PJ, Afonso CL (2012) Complete genome sequencing of a novel Newcastle disease virus isolate circulating in layer chickens in the Dominican Republic. J Virol 86:9550. CrossRefGoogle Scholar
  19. 19.
    Maminiaina OF, Gil P, Briand FX, Albina E, Keita D, Rasamoelina Andriamanivo H, Chevalier V, Lancelot R, Martinez D, Rakotondravao R, Rajaonarison JJ, Koko M, Andriantsimahavandy AA, Jestin V, Servan de Almeida R (2010) Newcastle disease virus in madagascar: identification of an original genotype possibly deriving from a died out ancestor of genotype IV. PLoS One 5:e13987. CrossRefGoogle Scholar
  20. 20.
    Munir M, Linde AM, Zohari S, Stahl K, Baule C, Engstrom B, Renstrom LHM, Berg M (2011) Whole genome sequencing and characterization of a virulent Newcastle disease virus isolated from an outbreak in Sweden. Virus Genes 43:261–271. CrossRefGoogle Scholar
  21. 21.
    Tsunekuni R, Ito H, Otsuki K, Kida H, Ito T (2010) Genetic comparisons between lentogenic Newcastle disease virus isolated from waterfowl and velogenic variants. Virus Genes 40:252–255. CrossRefGoogle Scholar
  22. 22.
    Cho SH, Kim SJ, Kwon HJ (2007) Genomic sequence of an antigenic variant Newcastle disease virus isolated in Korea. Virus Genes 35:293–302. CrossRefGoogle Scholar
  23. 23.
    Linde AM, Munir M, Zohari S, Stahl K, Baule C, Renström L, Berg M (2010) Complete genome characterisation of a Newcastle disease virus isolated during an outbreak in Sweden in 1997. Virus Genes 41:65–173. CrossRefGoogle Scholar
  24. 24.
    Wei D, Yang B, Li YL, Xue CF, Chen ZN, Bian H (2008) Characterization of the genome sequence of an oncolytic Newcastle disease virus strain Italien. Virus Res 135:312–319. CrossRefGoogle Scholar
  25. 25.
    Miller PJ, Kim LM, Ip HS, Afonso CL (2009) Evolutionary dynamics of Newcastle disease virus. Virology 391:64–72. CrossRefGoogle Scholar
  26. 26.
    Miller PJ, Decanini EL, Afonso CL (2010) Newcastle disease: evolution of genotypes and the related diagnostic challenges. Infect Genet Evol 10:26–35. CrossRefGoogle Scholar
  27. 27.
    Song Q, Cao Y, Li Q, Gu M, Zhong L, Hu S (2011) Artificial recombination may influence the evolutionary analysis of Newcastle disease virus. J Virol 85:10409–10414. CrossRefGoogle Scholar
  28. 28.
    Chong YL, Padhi A, Hudson PJ, Poss M (2010) The effect of vaccination on the evolution and population dynamics of avian paramyxovirus-1. PLoS Pathog 6:e1000872. CrossRefGoogle Scholar
  29. 29.
    Satharasinghe DA, Murulitharan K, Tan SW, Yeap SK, Munir M, Ideris A, Omar AR (2016) Detection of inter-lineage natural recombination in avian paramyxovirus serotype 1 using simplified deep sequencing platform. Front Microbiol 7:1907. CrossRefGoogle Scholar
  30. 30.
    Bush RM (2001) Predicting adaptive evolution. Nat Rev Genet 2:387–392. CrossRefGoogle Scholar
  31. 31.
    Kosiol C, Bofkin L, Whelan S (2006) Phylogenetics by likelihood: evolutionary modeling as a tool for understanding the genome. J Biomed Inform 39:51–61. CrossRefGoogle Scholar
  32. 32.
    Yang Z, Nielsen R (2002) Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol Biol Evol 19:908–917. CrossRefGoogle Scholar
  33. 33.
    Aldous EW, Mynn JK, Banks J, Alexander DJ (2003) A molecular epidemiological study of avian paramyxovirus type 1 (Newcastle disease virus) isolates by phylogenetic analysis of a partial nucleotide sequence of the fusion protein gene. Avian Pathol 32:239–257. CrossRefGoogle Scholar
  34. 34.
    Ballagi-Pordány A, Wehmann E, Herczeg J, Belák S, Lomniczi B (1996) Identification and grouping of Newcastle disease virus strains by restriction site analysis of a region from the F gene. Arch Virol 141:243–261. CrossRefGoogle Scholar
  35. 35.
    Czegledi A, Ujvari D, Somogyi E, Wehmann E, Werner O, Lomniczi B (2006) Third genome size category of avian paramyxovirus serotype 1 (Newcastle disease virus) and evolutionary implications. Virus Res 120:36–48. CrossRefGoogle Scholar
  36. 36.
    Diel DG, da Silva LHA, Liu H, Wang Z, Miller PJ, Afonso CL (2012) Genetic diversity of avian paramyxovirus type 1: proposal for a unified nomenclature and classification system of Newcastle disease virus genotypes. Infect Genet Evol 12:1770–1779. CrossRefGoogle Scholar
  37. 37.
    Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and clustal X version 2.0. Bioinformatics 23:2947–2948. CrossRefGoogle Scholar
  38. 38.
    Martin DP, Williamson C, Posada D (2005) RDP2: recombination detection and analysis from sequence alignments. Bioinformatics 21:260–262. CrossRefGoogle Scholar
  39. 39.
    Sawyer SA (1989) Statistical tests for detecting gene conversion. Mol Biol Evol 6:526–538. Google Scholar
  40. 40.
    Smith JM (1992) Analyzing the mosaic structure of genes. J Mol Evol 34:126–129Google Scholar
  41. 41.
    Posada D, Crandall KA (2001) Evaluation of methods for detecting recombination from DNA sequences: computer simulations. PNAS 98:13757–13762. CrossRefGoogle Scholar
  42. 42.
    Salminen MO, Carr JK, Burke DS, McCutchan FE (1995) Identification of breakpoints in intergenotypic recombinants of HIV type 1 by bootscanning. AIDS Res Hum Retrovir 11:1423–1425. CrossRefGoogle Scholar
  43. 43.
    Gibbs MJ, Armstrong JS, Gibbs AJ (2000) Sister-scanning: a Monte Carlo procedure for assessing signals in recombinant sequences. Bioinformatics 16:573–582. CrossRefGoogle Scholar
  44. 44.
    Boni MF, Posada D, Feldman MW (2007) An exact nonparametric method for inferring mosaic structure in sequence triplets. Genetics 176:1035–1047. CrossRefGoogle Scholar
  45. 45.
    Kosakovsky Pond SL, Frost SDW, Muse SV (2005) HyPhy: hypothesis testing using phylogenies. Bioinformatics 21:676–679. CrossRefGoogle Scholar
  46. 46.
    Charrel RN, de Lamballerie X, Fulhorst CF (2001) The Whitewater Arroyo virus: natural evidence for genetic recombination among Tacaribe serocomplex viruses (family Arenaviridae). Virology 283:161–166. CrossRefGoogle Scholar
  47. 47.
    Klempa B, Schmidt HA, Ulrich R, Kaluz S, Labuda M, Meisel H, Hjelle B, Kruger DH (2003) Genetic interaction between distinct Dobrava hantavirus subtypes in Apodemus agrarius and A. flavicollis in nature. J Virol 77:804–809CrossRefGoogle Scholar
  48. 48.
    Sibold C, Meisel H, Kruger DH, Labuda M, Lysy J, Kozuch O, Pejcoch M, Vaheri A, Plyusnin A (1999) Recombination in Tula hantavirus evolution: analysis of genetic lineages from Slovakia. J Virol 73:667–675Google Scholar
  49. 49.
    Park ES, Suzuki M, Kimura M, Maruyama K, Mizutani H, Saito R, Kubota N, Furuya T, Mizutani T, Imaoka K, Morikawa S (2014) Identification of a natural recombination in the F and H genes of feline morbillivirus. Virology 468–470:524–531. CrossRefGoogle Scholar
  50. 50.
    Qin Z, Sun L, Ma B, Cui Z, Zhu Y, Kitamura Y, Liu W (2008) F gene recombination between genotype II and VII Newcastle disease virus. Virus Res 131:299–303. CrossRefGoogle Scholar
  51. 51.
    Mayahi V, Esmaelizad M (2017) Molecular evolution and epidemiological links study of Newcastle disease virus isolates from 1995 to 2016 in Iran. Arch Virol 162:3727–3743. CrossRefGoogle Scholar
  52. 52.
    Afonso CL (2008) Not so fast on recombination analysis of newcastle disease virus. J Virol 82:9303. CrossRefGoogle Scholar
  53. 53.
    Rout SN, Samal SK (2008) The large polymerase protein is associated with the virulence of newcastle disease virus. J Virol 82:7828–7836. CrossRefGoogle Scholar
  54. 54.
    McGinnes L, Gravel K, Morrison T (2002) Newcastle disease virus HN protein alters the conformation of the F protein at cell surfaces. J Virol 76:12622–12633. CrossRefGoogle Scholar
  55. 55.
    Swanson K, Wen X, Leser GP, Paterson RG, Lamb RA, Jardetzky TS (2010) Structure of the Newcastle disease virus F protein in the post-fusion conformation. Virology 402:372–379. CrossRefGoogle Scholar
  56. 56.
    Gu M, Liu W, Xu L, Cao Y, Yao C, Hu S, Liu X (2011) Positive selection in the hemagglutinin-neuraminidase gene of Newcastle disease virus and its effect on vaccine efficacy. Virol J 8:150. CrossRefGoogle Scholar
  57. 57.
    Lam HY, Yeap SK, Rasoli M, Omar AR, Yusoff K, Suraini AA, Alitheen NB (2011) Safety and clinical usage of Newcastle disease virus in cancer therapy. J Biomed Biotechnol 2011:718710. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Central Laboratory Department, Razi Vaccine and Serum Research InstituteAgricultural Research, Education and Extension Organization (AREEO)KarajIran

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