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Independent evolution of porcine reproductive and respiratory syndrome virus 2 with genetic heterogeneity in antigenic regions of structural proteins in Korea

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Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen that affects the global swine industry. The continuous evolution of this virus has made control and prevention difficult, which emphasizes the importance of monitoring currently circulating PRRSV strains. In this study, we investigated the genetic characteristics of whole structural genes of 35 PRRSV-2 isolates that circulated between 2012 and 2017 in Korea. Genetic and phylogenetic analysis demonstrated that a recently identified PRRSV-2 shared a relatively low level of nucleotide sequence identity that ranged from 86.2% to 92.8%; however, they were clustered into four distinct Korean field clades, except KU-N1702, in ORF2–7-based phylogeny. KU-N1702 was closely related to the NADC30-like strains that were identified in the USA and China. Amino acid sequence analysis showed that the GP5 neutralizing epitope was conserved among the KU viruses. In contrast, the viruses had genetic mutations in key residues for viral neutralization within GP5 and M. For minor structural proteins, neutralizing epitopes, aa 41–55 of GP2, 61–75 of GP3, and 51–65 of GP4, were variable among the KU viruses. Bioinformatics demonstrated diversifying evolution within the GP2 and GP4 neutralizing epitopes and the emergence of a novel glycosylation site within the GP3 and GP4 neutralizing epitopes. Taken together, these data provide evidence that Korean PRRSV-2 evolved independently in Korea, with genetic heterogeneity in antigenic regions of structural proteins.

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References

  1. An TQ, Zhou YJ, Qiu HJ, Tong GZ, Wang YF, Liu JX, Yang JY (2005) Identification of a novel B cell epitope on the nucleocapsid protein of porcine reproductive and respiratory syndrome virus by phage display. Virus Genes 31:81–87

    Article  PubMed  CAS  Google Scholar 

  2. Ansari IH, Kwon B, Osorio FA, Pattnaik AK (2006) Influence of N-linked glycosylation of porcine reproductive and respiratory syndrome virus GP5 on virus infectivity, antigenicity, and ability to induce neutralizing antibodies. J Virol 80:3994–4004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Brar MS, Shi M, Murtaugh MP, Leung FC (2015) Evolutionary diversification of type 2 porcine reproductive and respiratory syndrome virus. J Gen Virol 96:1570–1580

    Article  PubMed  CAS  Google Scholar 

  4. Bush EJ, Corso B, Zimmerman J, Swenson S, Pyburn D, Burkgren T (1999) Update on the acute PRRS investigative study. Swine Health and Production 7:179

    Google Scholar 

  5. Cha SH, Choi EJ, Park JH, Yoon SR, Song JY, Kwon JH, Song HJ, Yoon KJ (2006) Molecular characterization of recent Korean porcine reproductive and respiratory syndrome (PRRS) viruses and comparison to other Asian PRRS viruses. Vet Microbiol 117:248–257

    Article  PubMed  CAS  Google Scholar 

  6. Choi E-J, Lee C-H, Song J-Y, Song H-J, Park C-K, Kim B, Shin Y-K (2013) Genetic diversity of porcine reproductive and respiratory syndrome virus in Korea. J Vet Sci 14:115

    Article  PubMed  PubMed Central  Google Scholar 

  7. Choi HW, Nam E, Lee YJ, Noh YH, Lee SC, Yoon IJ, Kim HS, Kang SY, Choi YK, Lee C (2014) Genomic analysis and pathogenic characteristics of Type 2 porcine reproductive and respiratory syndrome virus nsp2 deletion strains isolated in Korea. Vet Microbiol 170:232–245

    Article  PubMed  CAS  Google Scholar 

  8. Collins JE, Benfield DA, Christianson WT, Harris L, Hennings JC, Shaw DP, Goyal SM, McCullough S, Morrison RB, Joo HS et al (1992) Isolation of swine infertility and respiratory syndrome virus (isolate ATCC VR-2332) in North America and experimental reproduction of the disease in gnotobiotic pigs. J Vet Diagn Invest 4:117–126

    Article  PubMed  CAS  Google Scholar 

  9. Costers S, Vanhee M, Van Breedam W, Van Doorsselaere J, Geldhof M, Nauwynck HJ (2010) GP4-specific neutralizing antibodies might be a driving force in PRRSV evolution. Virus Res 154:104–113

    Article  PubMed  CAS  Google Scholar 

  10. Das PB, Dinh PX, Ansari IH, de Lima M, Osorio FA, Pattnaik AK (2010) The minor envelope glycoproteins GP2a and GP4 of porcine reproductive and respiratory syndrome virus interact with the receptor CD163. J Virol 84:1731–1740

    Article  PubMed  CAS  Google Scholar 

  11. Das PB, Vu HL, Dinh PX, Cooney JL, Kwon B, Osorio FA, Pattnaik AK (2011) Glycosylation of minor envelope glycoproteins of porcine reproductive and respiratory syndrome virus in infectious virus recovery, receptor interaction, and immune response. Virology 410:385–394

    Article  PubMed  CAS  Google Scholar 

  12. de Lima M, Pattnaik AK, Flores EF, Osorio FA (2006) Serologic marker candidates identified among B-cell linear epitopes of Nsp2 and structural proteins of a North American strain of porcine reproductive and respiratory syndrome virus. Virology 353:410–421

    Article  PubMed  CAS  Google Scholar 

  13. Delisle B, Gagnon CA, Lambert ME, D’Allaire S (2012) Porcine reproductive and respiratory syndrome virus diversity of Eastern Canada swine herds in a large sequence dataset reveals two hypervariable regions under positive selection. Infect Genet Evol 12:1111–1119

    Article  PubMed  Google Scholar 

  14. Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Fan B, Liu X, Bai J, Zhang T, Zhang Q, Jiang P (2015) The amino acid residues at 102 and 104 in GP5 of porcine reproductive and respiratory syndrome virus regulate viral neutralization susceptibility to the porcine serum neutralizing antibody. Virus Res 204:21–30

    Article  PubMed  CAS  Google Scholar 

  16. Fan B, Liu X, Bai J, Zhang T, Zhang Q, Jiang P (2016) Influence of the amino acid residues at 70 in M protein of porcine reproductive and respiratory syndrome virus on viral neutralization susceptibility to the serum antibody. Virol J 13:51

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Gupta R, Jung E, Brunak S (2004) Prediction of N-glycosylation sites in human proteins. http://www.cbs.dtu.dk/services/NetNGlyc

  18. Han J, Wang Y, Faaberg KS (2006) Complete genome analysis of RFLP 184 isolates of porcine reproductive and respiratory syndrome virus. Virus Res 122:175–182

    Article  PubMed  CAS  Google Scholar 

  19. Han M, Yoo D (2014) Engineering the PRRS virus genome: updates and perspectives. Vet Microbiol 174:279–295

    Article  PubMed  CAS  Google Scholar 

  20. Hanada K, Suzuki Y, Nakane T, Hirose O, Gojobori T (2005) The origin and evolution of porcine reproductive and respiratory syndrome viruses. Mol Biol Evol 22:1024–1031

    Article  PubMed  CAS  Google Scholar 

  21. Johnson CR, Griggs TF, Gnanandarajah J, Murtaugh MP (2011) Novel structural protein in porcine reproductive and respiratory syndrome virus encoded by an alternative ORF5 present in all arteriviruses. J Gen Virol 92:1107–1116

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Kapur V, Elam MR, Pawlovich TM, Murtaugh MP (1996) Genetic variation in porcine reproductive and respiratory syndrome virus isolates in the midwestern United States. J Gen Virol 77(Pt 6):1271–1276

    Article  PubMed  CAS  Google Scholar 

  23. Kuhn JH, Lauck M, Bailey AL, Shchetinin AM, Vishnevskaya TV, Bao Y, Ng TF, LeBreton M, Schneider BS, Gillis A, Tamoufe U, Diffo Jle D, Takuo JM, Kondov NO, Coffey LL, Wolfe ND, Delwart E, Clawson AN, Postnikova E, Bollinger L, Lackemeyer MG, Radoshitzky SR, Palacios G, Wada J, Shevtsova ZV, Jahrling PB, Lapin BA, Deriabin PG, Dunowska M, Alkhovsky SV, Rogers J, Friedrich TC, O’Connor DH, Goldberg TL (2016) Reorganization and expansion of the nidoviral family Arteriviridae. Arch Virol 161:755–768

    Article  PubMed  CAS  Google Scholar 

  24. Li J, Murtaugh MP (2012) Dissociation of porcine reproductive and respiratory syndrome virus neutralization from antibodies specific to major envelope protein surface epitopes. Virology 433:367–376

    Article  PubMed  CAS  Google Scholar 

  25. Mardassi H, Massie B, Dea S (1996) Intracellular synthesis, processing, and transport of proteins encoded by ORFs 5 to 7 of porcine reproductive and respiratory syndrome virus. Virology 221:98–112

    Article  PubMed  CAS  Google Scholar 

  26. Murtaugh MP, Elam MR, Kakach LT (1995) Comparison of the structural protein coding sequences of the VR-2332 and Lelystad virus strains of the PRRS virus. Arch Virol 140:1451–1460

    Article  PubMed  CAS  Google Scholar 

  27. Murtaugh MP, Stadejek T, Abrahante JE, Lam TT, Leung FC (2010) The ever-expanding diversity of porcine reproductive and respiratory syndrome virus. Virus Res 154:18–30

    Article  PubMed  CAS  Google Scholar 

  28. Ostrowski M, Galeota JA, Jar AM, Platt KB, Osorio FA, Lopez OJ (2002) Identification of neutralizing and nonneutralizing epitopes in the porcine reproductive and respiratory syndrome virus GP5 ectodomain. J Virol 76:4241–4250

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Pirzadeh B, Dea S (1997) Monoclonal antibodies to the ORF5 product of porcine reproductive and respiratory syndrome virus define linear neutralizing determinants. J Gen Virol 78(Pt 8):1867–1873

    Article  PubMed  CAS  Google Scholar 

  30. Pond SL, Frost SD (2005) Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21:2531–2533

    Article  PubMed  CAS  Google Scholar 

  31. Shi M, Lam TT, Hon CC, Murtaugh MP, Davies PR, Hui RK, Li J, Wong LT, Yip CW, Jiang JW, Leung FC (2010) Phylogeny-based evolutionary, demographical, and geographical dissection of North American type 2 porcine reproductive and respiratory syndrome viruses. J Virol 84:8700–8711

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Tian D, Wei Z, Zevenhoven-Dobbe JC, Liu R, Tong G, Snijder EJ, Yuan S (2012) Arterivirus minor envelope proteins are a major determinant of viral tropism in cell culture. J Virol 86:3701–3712

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Tian K (2017) NADC30-like porcine reproductive and respiratory syndrome in China. Open Virol J 11:59–65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Tong GZ, Zhou YJ, Hao XF, Tian ZJ, An TQ, Qiu HJ (2007) Highly pathogenic porcine reproductive and respiratory syndrome, China. Emerg Infect Dis 13:1434–1436

    Article  PubMed  PubMed Central  Google Scholar 

  36. Trible BR, Popescu LN, Monday N, Calvert JG, Rowland RR (2015) A single amino acid deletion in the matrix protein of porcine reproductive and respiratory syndrome virus confers resistance to a polyclonal swine antibody with broadly neutralizing activity. J Virol 89:6515–6520

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Vanhee M, Costers S, Van Breedam W, Geldhof MF, Van Doorsselaere J, Nauwynck HJ (2010) A variable region in GP4 of European-type porcine reproductive and respiratory syndrome virus induces neutralizing antibodies against homologous but not heterologous virus strains. Viral Immunol 23:403–413

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Vanhee M, Van Breedam W, Costers S, Geldhof M, Noppe Y, Nauwynck H (2011) Characterization of antigenic regions in the porcine reproductive and respiratory syndrome virus by the use of peptide-specific serum antibodies. Vaccine 29:4794–4804

    Article  PubMed  CAS  Google Scholar 

  39. Vashisht K, Goldberg TL, Husmann RJ, Schnitzlein W, Zuckermann FA (2008) Identification of immunodominant T-cell epitopes present in glycoprotein 5 of the North American genotype of porcine reproductive and respiratory syndrome virus. Vaccine 26:4747–4753

    Article  PubMed  CAS  Google Scholar 

  40. Vu HL, Kwon B, Yoon KJ, Laegreid WW, Pattnaik AK, Osorio FA (2011) Immune evasion of porcine reproductive and respiratory syndrome virus through glycan shielding involves both glycoprotein 5 as well as glycoprotein 3. J Virol 85:5555–5564

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Wang Q, Chen J, Peng J, An T, Leng C, Sun Y, Guo X, Ge X, Tian Z, Yang H (2014) Characterisation of novel linear antigen epitopes on North American-type porcine reproductive and respiratory syndrome virus M protein. Arch Virol 159:3021–3028

    Article  PubMed  CAS  Google Scholar 

  42. Wang Q, Peng J, Sun Y, Chen J, An T, Leng C, Li L, Zhao H, Guo X, Ge X, Yang H, Tian Z (2014) Unique epitopes recognized by monoclonal antibodies against HP-PRRSV: deep understanding of antigenic structure and virus-antibody interaction. PLoS One 9:e111633

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Wang YX, Zhou YJ, Li GX, Zhang SR, Jiang YF, Xu AT, Yu H, Wang MM, Yan LP, Tong GZ (2011) Identification of immunodominant T-cell epitopes in membrane protein of highly pathogenic porcine reproductive and respiratory syndrome virus. Virus Res 158:108–115

    Article  PubMed  CAS  Google Scholar 

  44. Wensvoort G, Terpstra C, Pol JM, ter Laak EA, Bloemraad M, de Kluyver EP, Kragten C, van Buiten L, den Besten A, Wagenaar F et al (1991) Mystery swine disease in The Netherlands: the isolation of Lelystad virus. Vet Q 13:121–130

    Article  PubMed  CAS  Google Scholar 

  45. Wootton SK, Nelson EA, Yoo D (1998) Antigenic structure of the nucleocapsid protein of porcine reproductive and respiratory syndrome virus. Clin Diagn Lab Immunol 5:773–779

    PubMed  PubMed Central  CAS  Google Scholar 

  46. Wu WH, Fang Y, Farwell R, Steffen-Bien M, Rowland RR, Christopher-Hennings J, Nelson EA (2001) A 10-kDa structural protein of porcine reproductive and respiratory syndrome virus encoded by ORF2b. Virology 287:183–191

    Article  PubMed  CAS  Google Scholar 

  47. Yang L, Frey ML, Yoon KJ, Zimmerman JJ, Platt KB (2000) Categorization of North American porcine reproductive and respiratory syndrome viruses: epitopic profiles of the N, M, GP5 and GP3 proteins and susceptibility to neutralization. Arch Virol 145:1599–1619

    Article  PubMed  CAS  Google Scholar 

  48. Zhou YJ, Yu H, Tian ZJ, Liu JX, An TQ, Peng JM, Li GX, Jiang YF, Cai XH, Xue Q, Wang M, Wang YF, Tong GZ (2009) Monoclonal antibodies and conserved antigenic epitopes in the C terminus of GP5 protein of the North American type porcine reproductive and respiratory syndrome virus. Vet Microbiol 138:1–10

    Article  PubMed  CAS  Google Scholar 

  49. Zimmerman JJ, Benfield DA, Scott AD, Murtaugh MP, Stadejek T, Stevenson GW, Torremorell M (2012) Porcine reproductive and respiratory syndrome virus (porcine arterivirus). In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW (eds) Diseases of swine, 10th edn. Wiley-Blackwell, Hoboken, pp 387–418

    Google Scholar 

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Acknowledgements

This work was partially supported by Optipharm Inc., Cheongju, Republic of Korea and by Konkuk University in 2017.

Funding

This study was supported by Optipharm Inc., Cheongju, Republic of Korea and Konkuk University in 2017.

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Correspondence to Young S. Lyoo.

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Handling Editor: Zhenhai Chen.

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Kwon, T., Yoo, S.J., Sunwoo, S.Y. et al. Independent evolution of porcine reproductive and respiratory syndrome virus 2 with genetic heterogeneity in antigenic regions of structural proteins in Korea. Arch Virol 164, 213–224 (2019). https://doi.org/10.1007/s00705-018-4048-7

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  • DOI: https://doi.org/10.1007/s00705-018-4048-7

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