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Nsp2 and GP5-M of Porcine Reproductive and Respiratory Syndrome Virus Contribute to Targets for Neutralizing Antibodies

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is characterized by its genetic variation and limited cross protection among heterologous strains. Even though several viral structural proteins have been regarded as inducers of neutralizing antibodies (NAs) against PRRSV, the mechanism underlying limited cross-neutralization among heterologous strains is still controversial. In the present study, examinations of NA cross reaction between a highly pathogenic PRRSV (HP-PRRSV) strain, JXwn06, and a low pathogenic PRRSV (LP-PRRSV) strain, HB-1/3.9, were conducted with viral neutralization assays in MARC-145 cells. None of the JXwn06-hyperimmuned pigs’ sera could neutralize HB-1/3.9 in vitro and vice versa. To address the genetic variation between these two viruses that are associated with limited cross-neutralization, chimeric viruses with coding regions swapped between these two strains were constructed. Viral neutralization assays indicated that variations in nonstructural protein 2 (nsp2) and structural proteins together contribute to weak cross-neutralization activity between JXwn06 and HB-1/3.9. Furthermore, we substituted the nsp2-, glycoprotein2 (GP2)-, GP3-, and GP4-coding regions together, or nsp2-, GP5-, and membrane (M) protein-coding regions simultaneously between these two viruses to construct chimeric viruses to test cross-neutralization reactivity with hyperimmunized sera induced by their parental viruses. The results indicated that the swapped nsp2 and GP5-M viruses increased the neutralization reactivity with the donor strain antisera in MARC-145 cells. Taken together, these results show that variations in nsp2 and GP5-M correlate with the limited neutralization reactivity between the heterologous strains HP-PRRSV JXwn06 and LP-PRRSV HB-1/3.9.

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Acknowledgements

This study was supported by the Major Program of National Natural Science Foundation of China (31490603, 31572549) and the National Key Technology R & D Program of China (2015BAD12B01-2).

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Authors

Contributions

JS, XG, LZ, XNG, JH and HY contributed to the study design. JS, BH and XZ performed the experiments in the study. XG, LZ and JS analyzed the data. JS, LZ and XG wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xin Guo.

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The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

The animal experiments in this study were approved by The Laboratory Animal Ethical Committee of China Agricultural University. All institutional and national guidelines for the care and use of animals were followed.

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Su, J., Zhou, L., He, B. et al. Nsp2 and GP5-M of Porcine Reproductive and Respiratory Syndrome Virus Contribute to Targets for Neutralizing Antibodies. Virol. Sin. 34, 631–640 (2019). https://doi.org/10.1007/s12250-019-00149-6

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  • DOI: https://doi.org/10.1007/s12250-019-00149-6

Keywords

  • Porcine reproductive and respiratory syndrome virus (PRRSV)
  • Neutralizing antibody (NA)
  • Non-structural protein 2 (nsp2)
  • Structural proteins (SPs)