1887

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a major problem in the pork industry worldwide. The limitations of current PRRSV vaccines require the development of a new generation of vaccines. One of the key steps in future vaccine development is to include markers for diagnostic differentiation of vaccinated animals from those naturally infected with wild-type virus. Using a cDNA infectious clone of type 1 PRRSV, this study constructed a recombinant green fluorescent protein (GFP)-tagged PRRSV containing a deletion of an immunogenic epitope, ES4, in the nsp2 region. In a nursery pig disease model, the recombinant virus was attenuated with a lower level of viraemia in comparison with that of the parental virus. To complement the marker identification, GFP and ES4 epitope-based ELISAs were developed. Pigs immunized with the recombinant virus lacked antibodies directed against the corresponding deleted epitope, but generated a high-level antibody response to GFP by 14 days post-infection. These results demonstrated that this recombinant marker virus, in conjunction with the diagnostic tests, enables serological differentiation between marker virus-infected animals and those infected with the wild-type virus. This rationally designed marker virus will provide a basis for further development of PRRSV marker vaccines to assist with the control of PRRS.

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2008-12-01
2021-08-05
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References

  1. Allende R., Lewis T. L., Lu Z., Rock D. L., Kutish G. F., Ali A., Doster A. R., Osorio F. A. 1999; North American and European porcine reproductive and respiratory syndrome viruses differ in non-structural protein coding regions. J Gen Virol 80:307–315
    [Google Scholar]
  2. Babiuk L. A. 1999; Broadening the approaches to developing more effective vaccines. Vaccine 17:1587–1595 [CrossRef]
    [Google Scholar]
  3. Babiuk L. A., Lewis J., Suradhat S., Baca-Estrada M., Foldvari M., Babiuk S. 1999; Polynucleotide vaccines: potential for inducing immunity in animals. J Biotechnol 73:131–140 [CrossRef]
    [Google Scholar]
  4. Babiuk L. A., Babiuk S. L., Baca-Estrada M. E. 2002; Novel vaccine strategies. Adv Virus Res 58:29–80
    [Google Scholar]
  5. Barrett T., Parida S., Mohapatra M., Walsh P., Das S., Baron M. D. 2003; Development of new generation rinderpest vaccines. Dev Biol (Basel 114:89–97
    [Google Scholar]
  6. Bautista E. M., Goyal S. M., Soon I. J., Joo H. S., Collins J. E. 1996; Structural polypeptides of the American (VR-2332) strain of porcine reproductive and respiratory syndrome virus. Arch Virol 141:1357–1365 [CrossRef]
    [Google Scholar]
  7. Bosch J. C., Kaashoek M. J., Kroese A. H., Van Oirschot J. T. 1996; An attenuated bovine herpesvirus 1 marker vaccine induces a better protection than two inactivated marker vaccines. Vet Microbiol 52:223–234 [CrossRef]
    [Google Scholar]
  8. Castillo-Olivares J., Wieringa R., Bakonyi T., de Vries A. A., Davis-Poynter N. J., Rottier P. J. 2003; Generation of a candidate live marker vaccine for equine arteritis virus by deletion of the major virus neutralization domain. J Virol 77:8470–8480 [CrossRef]
    [Google Scholar]
  9. de Lima M., Pattnaik A. K., Flores E. F., Osorio F. A. 2006; Mapping of B-cell linear epitopes on Nsp2 and structural proteins of a North American strain of porcine reproductive and respiratory syndrome virus. Virology 353:410–421 [CrossRef]
    [Google Scholar]
  10. de Lima M., Kwon B., Ansari I. H., Pattnaik A. K., Flores E. F., Osorio F. A. 2008; Development of a porcine reproductive and respiratory syndrome virus differentiable (DIVA) strain through deletion of specific immunodominant epitopes. Vaccine 26:3594–3600 [CrossRef]
    [Google Scholar]
  11. den Boon J. A., Faaberg K. S., Meulenberg J. J. M., Wassenaar A. L. M., Plagemann P. G. W., Gorbelenya A. E., Snijder E. J. 1995; Processing and evolution of the N-terminal region of the arterivirus replicase ORF1a protein: identification of two papainlike cysteine proteases. J Virol 69:4500–4505
    [Google Scholar]
  12. Dong X. N., Chen Y. H. 2007; Marker vaccine strategies and candidate CSFV marker vaccines. Vaccine 25:205–230 [CrossRef]
    [Google Scholar]
  13. Fang Y., Kim D. Y., Ropp S., Steen P., Christopher-Hennings J., Nelson E. A., Rowland R. R. R. 2004; Heterogeneity in Nsp2 of European-like porcine reproductive and respiratory syndrome viruses isolated in the United States. Virus Res 100:229–235 [CrossRef]
    [Google Scholar]
  14. Fang Y., Rowland R. R. R., Roof M., Lunney J. K., Christopher-Hennings J., Nelson E. A. 2006; A full-length cDNA infectious clone of North American type 1 porcine reproductive and respiratory syndrome virus: expression of green fluorescent protein in the Nsp2 region. J Virol 80:11447–11455 [CrossRef]
    [Google Scholar]
  15. Fang Y., Schneider P., Zhang W. P., Faaberg K., Nelson E. A., Rowland R. R. R. 2007; Diversity and evolution of a newly emerged North American Type 1 porcine arterivirus. Arch Virol 152:1009–1017 [CrossRef]
    [Google Scholar]
  16. Ferrin N. H., Fang Y., Johnson C. R., Murtaugh M. P., Polson D. D., Torremorell M., Gramer M. L., Nelson E. A. 2004; Validation of a blocking ELISA for the detection of antibodies against porcine reproductive and respiratory syndrome virus. Clin Diagn Lab Immunol 11:503–514
    [Google Scholar]
  17. Floegel-Niesmann G. 2003; Marker vaccines and companion diagnostic tests for classical swine fever. Dev Biol (Basel) 114:185–191
    [Google Scholar]
  18. Frias-Staheli N., Glannakopoulos N. V., Kikkert M., Taylor S. L., Bridgen A., Paragas J., Richt J. A., Rowland R. R. R., Schmaljohn C. S. other authors 2007; Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. Cell Host Microbe 2:404–416 [CrossRef]
    [Google Scholar]
  19. Gao Z. Q., Guo X., Yang H. C. 2004; Genomic characterization of two Chinese isolates of Porcine respiratory and reproductive syndrome virus . Arch Virol 149:1341–1351
    [Google Scholar]
  20. Han J., Liu G., Wang Y., Faaberg K. S. 2007; Identification of nonessential regions of the nsp2 replicase protein of porcine reproductive and respiratory syndrome virus strain VR-2332 for replication in cell culture. J Virol 81:9878–9890 [CrossRef]
    [Google Scholar]
  21. Hayashi N., Welschof M., Zewe M., Braunagel M., Dübel S., Breitling F., Little M. 1994; Simultaneous mutagenesis of antibody CDR regions by overlap extension and PCR. Biotechniques 17:310–315
    [Google Scholar]
  22. Hopp T. P., Woods K. R. 1981; Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A 78:3824–3828 [CrossRef]
    [Google Scholar]
  23. Kaashoek M. J., Moerman A., Madic J., Rijsewijk F. A., Quak J., Gielkens A. L., van Oirschot J. T. 1994; A conventionally attenuated glycoprotein E-negative strain of bovine herpesvirus type 1 is an efficacious and safe vaccine. Vaccine 12:439–444 [CrossRef]
    [Google Scholar]
  24. Kim D. Y., Calvert J. G., Chang K. O., Horlen K., Kerrigan M., Rowland R. R. R. 2007; Expression and stability of foreign tags inserted into nsp2 of porcine reproductive and respiratory syndrome virus (PRRSV). Virus Res 128:106–114 [CrossRef]
    [Google Scholar]
  25. Labarque G., Van Reeth K., Nauwynck H., Drexler C., Van Gucht S., Pensaert M. 2004; Impact of genetic diversity of European-type porcine reproductive and respiratory syndrome virus strains on vaccine efficacy. Vaccine 22:4183–4190 [CrossRef]
    [Google Scholar]
  26. Lawson S., Fang Y., Rowland R. R. R., Christopher-Hennings J., Nelson E. A. 2005; Experimental infection of pigs with European-like (Type 1) PRRSV isolates of US origin. In The 86th Annual Meeting of the Conference of Research Workers in Animal Diseases abstract no: 994–6 December 2005 St Louis; Missouri, USA:
    [Google Scholar]
  27. Mardassi H., Massive 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 [CrossRef]
    [Google Scholar]
  28. Martelli P., Cordioli P., Alborali L. G., Gozio S., De Angelis E., Ferrari L., Lombardi G., Borghetti P. 2007; Protection and immune response in pigs intradermally vaccinated against porcine reproductive and respiratory syndrome (PRRS) and subsequently exposed to a heterologous European (Italian cluster) field strain. Vaccine 25:3400–3408 [CrossRef]
    [Google Scholar]
  29. Mebatsion T., Koolen M. J. M., de Vaan L. T. C., de Haas N., Braber M., Romer-Oberdorfer A., van den Elzen P., van der Marel P. 2002; Newcastle disease virus marker vaccine: an immunodominant epitope on the nucleoprotein gene of NDV can be deleted or replaced by a foreign epitope. J Virol 76:10138–10146 [CrossRef]
    [Google Scholar]
  30. Meng X. J., Paul P. S., Morozov I., Halbur P. G. 1996; A nested set of six or seven subgenomic mRNAs is formed in cells infected with different isolates of porcine reproductive and respiratory syndrome virus. J Gen Virol 77:1265–1270 [CrossRef]
    [Google Scholar]
  31. Mengeling W. L., Lager K. M., Vorwald A. C. 1999; Safety and efficacy of vaccination of pregnant gilts against porcine reproductive and respiratory syndrome. Am J Vet Res 60:796–801
    [Google Scholar]
  32. Meulenberg J. J., Petersen-den Besten A. 1996; Identification and characterization of a sixth structural protein of Lelystad virus: the glycoprotein GP2 encoded by ORF2 is incorporated in virus particles. Virology 225:44–51 [CrossRef]
    [Google Scholar]
  33. Meulenberg J. J., Hulst M. M., de Meijer E. J., Moonen P. L., den Besten A., de Kluyver E. P., Wensvoort G., Moormann R. J. 1993; Lelystad virus, the causative agent of porcine epidemic abortion and respiratory syndrome (PEARS), is related to LDV and EAV. Virology 192:62–72 [CrossRef]
    [Google Scholar]
  34. Meulenberg J. J., Petersen-den Besten A., de Kluyver A., Moormann E. P., Schaaper R. J. M., Wensvoort G. 1995; Characterization of proteins encoded by ORFs 2 to 7 of Lelystad virus. Virology 206:155–163 [CrossRef]
    [Google Scholar]
  35. Moormann R. J., de Rover T., Briaire J., Peeters B. P., Gielkens A. L., van Oirschot J. T. 1990; Inactivation of the thymidine kinase gene of a g1 deletion mutant of pseudorabies virus generates a safe but still highly immunogenic vaccine strain. J Gen Virol 71:1591–1595 [CrossRef]
    [Google Scholar]
  36. Mounir S., Mardassi H., Dea S. 1995; Identification and characterization of the porcine reproductive and respiratory virus ORFs 7, 5 and 4 products. Adv Exp Med Biol 380:317–320
    [Google Scholar]
  37. Nelsen C. J., Murtaugh M. P., Faaberg K. S. 1999; Porcine reproductive and respiratory syndrome virus comparison: divergent evolution on two continents. J Virol 73:270–280
    [Google Scholar]
  38. Nelson E. A., Christopher-Hennings J., Wensvoort G., Collins J. E., Benfield D. A. 1993; Differentiation of United States and European isolates of porcine reproductive and respiratory syndrome (PRRS) virus using monoclonal antibodies. J Clin Microbiol 31:3184–3189
    [Google Scholar]
  39. Neumann E. J., Kliebenstein J. B., Johnson C. D., Mabry J. W., Bush E. J., Seitzinger A. H., Green A. L., Zimmerman J. J. 2005; Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. J Am Vet Med Assoc 227:385–392 [CrossRef]
    [Google Scholar]
  40. Oleksiewicz M. B., Botner A., Toft P., Normann P., Storgaard T. 2001; Epitope mapping porcine reproductive and respiratory syndrome virus by phage display: the nsp2 fragment of the replicase polyprotein contains a cluster of B-cell epitopes. J Virol 75:3277–3290 [CrossRef]
    [Google Scholar]
  41. Osorio F. A., Zuckermann F., Wills R., Meier W., Christian S., Galeota J., Doster A. 1998; PRRSV: comparison of commercial vaccines in their ability to induce protection against current PRRSV strains of high virulence. Allen D Leman Swine Conf 25:176–182
    [Google Scholar]
  42. Ran Z. G., Chen X. Y., Guo X., Ge X. N., Yoon K. J., Yang H. C. 2008; Recovery of viable porcine reproductive and respiratory syndrome virus from an infectious clone containing a partial deletion within the Nsp2-encoding region. Arch Virol 153:899–907 [CrossRef]
    [Google Scholar]
  43. Ropp S. L., Mahlum Wees C. E., Fang Y., Nelson E. A., Rossow K. D., Bien M., Arndt B., Preszler S., Steen P. other authors 2004; Characterization of emerging European-like PRRSV isolates in the United States. J Virol 78:3684–3703 [CrossRef]
    [Google Scholar]
  44. Shen S., Kwang J., Liu W., Liu D. X. 2000; Determination of the complete nucleotide sequence of a vaccine strain of porcine reproductive and respiratory syndrome virus and identification of the Nsp2 gene with a unique insertion. Arch Virol 145:871–883 [CrossRef]
    [Google Scholar]
  45. Snijder E. J., Meulenberg J. J. 1998; The molecular biology of arteriviruses. J Gen Virol 79:961–979
    [Google Scholar]
  46. Snijder E. J., Wassenaar A. L. M., Spaan W. J. M. 1994; Proteolytic processing of the replicase ORF1a protein of equine arteritis virus. J Virol 68:5755–5764
    [Google Scholar]
  47. Snijder E. J., Wassenaar A. L. M., Spaan W. J., Gorbalenya A. E. 1995; The arterivirus Nsp2 protease. An unusual cysteine protease with primary structure similarities to both papain-like and chymotrypsin-like proteases. J Biol Chem 270:16671–16676 [CrossRef]
    [Google Scholar]
  48. Sun T., Lu P., Wang X. 2004; Localization of infection-related epitopes on the non-structural protein 3ABC of foot-and-mouth disease virus and the application of tandem epitopes. J Virol Methods 119:79–86 [CrossRef]
    [Google Scholar]
  49. Tian K., Yu X., Zhao T., Feng Y., Cao Z., Wang C., Hu Y., Chen X., Hu D. other authors 2007; Emergence of fatal PRRSV variants: unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark. PLoS ONE 2:e526 [CrossRef]
    [Google Scholar]
  50. van Gennip H. G., Bouma A., van Rijn P. A., Widjojoatmodjo M. N., Moormann R. J. 2002; Experimental non-transmissible marker vaccines for classical swine fever (CSF) by trans -complementation of Erns or E2 of CSFV. Vaccine 20:1544–1556 [CrossRef]
    [Google Scholar]
  51. van Oirschot J. T. 1999; Diva vaccines that reduce virus transmission. J Biotechnol 73:195–205 [CrossRef]
    [Google Scholar]
  52. van Oirschot J. T. 2001; Present and future of veterinary viral vaccinology: a review. Vet Q 23:100–108 [CrossRef]
    [Google Scholar]
  53. van Oirschot J. T., Kaashoek M. J., Rijsewijk F. A., Stegeman J. A. 1996; The use of marker vaccines in eradication of herpesviruses. J Biotechnol 44:75–81 [CrossRef]
    [Google Scholar]
  54. Walsh E. P., Baron M. D., Rennie L. F., Anderson J., Barrett T. 2000a; Development of a genetically marked recombinant rinderpest vaccine expressing green fluorescent protein. J Gen Virol 81:709–718
    [Google Scholar]
  55. Walsh E. P., Baron M. D., Rennie L. F., Monaghan P., Anderson J., Barrett T. 2000b; Recombinant rinderpest vaccines expressing membrane-anchored proteins as genetic markers: evidence of exclusion of marker protein from the virus envelope. J Virol 74:10165–10175 [CrossRef]
    [Google Scholar]
  56. Wasilk A., Callahan J., Christopher-Hennings J., Gay B. T., Fang Y., Dammen M., Reos M. E., Torremorell M., Polson D. other authors 2004; Detection of U.S. and Lelystad/European-like porcine reproductive and respiratory syndrome virus and relative quantitation in boar semen and serum by real-time PCR. J Clin Microbiol 42:4453–4461 [CrossRef]
    [Google Scholar]
  57. Wassenaar A. L., Spaan W. J., Gorbalenya A. E., Snijder E. J. 1997; Alternative proteolytic processing of the arterivirus replicase ORF1a polyprotein: evidence that Nsp2 acts as a cofactor for the Nsp4 serine protease. J Virol 71:9313–9322
    [Google Scholar]
  58. Widjojoatmodjo M. N., van Gennip H. G., Bouma A., van Rijn P. A., Moormann R. J. 2000; Classical swine fever virus Erns deletion mutants: trans -complementation and potential use as non transmissible, modified, live-attenuated marker vaccines. J Virol 74:2973–2980 [CrossRef]
    [Google Scholar]
  59. Wu W. H., Fang Y., Farwell R., Steffen-Bien M., Rowland R. R. R., Christopher-Hennings J., Nelson E. A. 2001; A 10-kDa structural protein of porcine reproductive and respiratory syndrome virus encoded by ORF 2b. Virology 287:183–191 [CrossRef]
    [Google Scholar]
  60. Wu W. H., Fang Y., Rowland R. R. R., Lawson S. R., Christopher-Hennings J., Yoon K. J., Nelson E. A. 2005; The 2b protein as a minor structural component of PRRSV. Virus Res 114:177–181 [CrossRef]
    [Google Scholar]
  61. Yuan S., Murtaugh M. P., Schumann F. A., Mickelson D., Faaberg K. S. 2004; Characterization of heteroclite subgenomic RNAs associated with PRRSV infection. Virus Res 105:75–87 [CrossRef]
    [Google Scholar]
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