Improved vaccine against PRRSV: Current Progress and future perspective

Frontiers in Microbiology

Volumn 8, Issue AUG, 2017, Pages

  Nan, Yuchen ^a   Wu, Chunyan ^a   Gu, Guoqian ^a   Sun, Weiyao ^a   Zhang, Yan Jin ^b   Zhou, En Min ^a  

^a NORTHWEST A F UNIVERSITY   (China)

^b UNIVERSITY OF MARYLAND   (United States)

Author keywords

Cross protection; Interferon; Modified live virus; Porcine reproductive and respiratory syndrome virus; PRRSV; PRRSV vaccine

Indexed keywords

EID: 85028371244     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2017.01635     Document Type: Review

References (186)

1. Adams, M. J., Lefkowitz, E. J., King, A. M., Harrach, B., Harrison, R. L., Knowles, N. J., et al. (2016). Ratification vote on taxonomic proposals to the international committee on taxonomy of viruses (2016). Arch. Virol. 161, 2921-2949. doi: 10.1007/s00705-016-2977-6
2. Albina, E., Carrat, C., and Charley, B. (1998). Interferon-alpha response to swine arterivirus (PoAV), the porcine reproductive and respiratory syndrome virus. J. Interferon Cytokine Res. 18, 485-490. doi: 10.1089/jir.1998. 18.485
3. An, T. Q., Tian, Z. J., Leng, C. L., Peng, J. M., and Tong, G. Z. (2011). Highly pathogenic porcine reproductive and respiratory syndrome virus, Asia. Emerg. Infect. Dis. 17, 1782-1784. doi: 10.3201/eid1709.110411
4. Bai, X., Wang, Y., Xu, X., Sun, Z., Xiao, Y., Ji, G., et al. (2016). Commercial vaccines provide limited protection to NADC30-like PRRSV infection. Vaccine 34, 5540-5545. doi: 10.1016/j.vaccine.2016.09.048
5. Balasuriya, U. B., and MacLachlan, N. J. (2004). The immune response to equine arteritis virus: potential lessons for other arteriviruses. Vet. Immunol. Immunopathol. 102, 107-129. doi: 10.1016/j.vetimm.2004.09.003
6. Bassaganya-Riera, J., Thacker, B. J., Yu, S., Strait, E., Wannemuehler, M. J., and Thacker, E. L. (2004). Impact of immunizations with porcine reproductive and respiratory syndrome virus on lymphoproliferative recall responses of CD8C T cells. Viral Immunol. 17, 25-37. doi: 10.1089/088282404322875430
7. Bastos, R. G., Dellagostin, O. A., Barletta, R. G., Doster, A. R., Nelson, E., Zuckermann, F., et al. (2004). Immune response of pigs inoculated with Mycobacterium bovis BCG expressing a truncated form of GP5 and M protein of porcine reproductive and respiratory syndrome virus. Vaccine 22, 467-474. doi: 10.1016/S0264-410X(03)00572-3
8. Baumann, A., Mateu, E., Murtaugh, M. P., and Summerfield, A. (2013). Impact of genotype 1 and 2 of porcine reproductive and respiratory syndrome viruses on interferon-alpha responses by plasmacytoid dendritic cells. Vet. Res. 44:33. doi: 10.1186/1297-9716-44-33
9. Benfield, D. A., Nelson, E., Collins, J. E., Harris, L., Goyal, S. M., Robison, D., et al. (1992). Characterization of swine infertility and respiratory syndrome (SIRS) virus (isolate ATCC VR-2332). J. Vet. Diagn. Invest. 4, 127-133. doi: 10.1177/104063879200400202
10. Binjawadagi, B., Dwivedi, V., Manickam, C., Ouyang, K., Torrelles, J. B., and Renukaradhya, G. J. (2014a). An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination. Int. J. Nanomed. 9, 1519-1535. doi: 10.2147/IJN.S59924
11. Binjawadagi, B., Dwivedi, V., Manickam, C., Ouyang, K., Wu, Y., Lee, L. J., et al. (2014b). Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs. Int. J. Nanomed. 9, 679-694. doi: 10.2147/IJN.S56127
12. Botner, A., Strandbygaard, B., Sorensen, K. J., Have, P., Madsen, K. G., Madsen, E. S., et al. (1997). Appearance of acute PRRS-like symptoms in sow herds after vaccination with a modified live PRRS vaccine. Vet Rec. 141, 497-499. doi: 10.1136/vr.141.19.497
13. Brockmeier, S. L., Loving, C. L., Vorwald, A. C., Kehrli, M. E. Jr., Baker, R. B., Nicholson, T. L., et al., (2012). Genomic sequence and virulence comparison of four Type 2 porcine reproductive and respiratory syndrome virus strains. Virus Res. 169, 212-221. doi: 10.1016/j.virusres.2012.07.030
14. Burkard, C., Lillico, S. G., Reid, E., Jackson, B., Mileham, A. J., Ait-Ali, T., et al. (2017). Precision engineering for PRRSV resistance in pigs: macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function. PLoS Pathog. 13:e1006206. doi: 10.1371/journal.ppat.1006206
15. Burton, D. R., Pyati, J., Koduri, R., Sharp, S. J., Thornton, G. B., Parren, P. W., et al. (1994). Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 266, 1024-1027. doi: 10.1126/science. 7973652
16. Butler, J. E., Lager, K. M., Golde, W., Faaberg, K. S., Sinkora, M., Loving, C., et al. (2014). Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic. Immunol. Res. 59, 81-108. doi: 10.1007/s12026-014- 8549-5
17. Calarese, D. A., Scanlan, C. N., Zwick, M. B., Deechongkit, S., Mimura, Y., Kunert, R., et al. (2003). Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science 300, 2065-2071. doi: 10. 1126/science.1083182
18. Calvert, J. G., Slade, D. E., Shields, S. L., Jolie, R.,Mannan, R. M., Ankenbauer, R. G., et al. (2007). CD163 expression confers susceptibility to porcine reproductive and respiratory syndrome viruses. J. Virol. 81, 7371-7379. doi: 10.1128/JVI. 00513-07
19. Cancel-Tirado, S. M., Evans, R. B., and Yoon, K. J. (2004). Monoclonal antibody analysis of porcine reproductive and respiratory syndrome virus epitopes associated with antibody-dependent enhancement and neutralization of virus infection. Vet. Immunol. Immunopathol. 102, 249-262. doi: 10.1016/j.vetimm. 2004.09.017
20. Carman, S., Sanford, S. E., and Dea, S. (1995). Assessment of seropositivity to porcine reproductive and respiratory syndrome (PRRS) virus in swine herds in Ontario-1978 to 1982. Can. Vet. J. 36, 776-777.
21. Chang, H. C., Peng, Y. T., Chang, H. L., Chaung, H. C., and Chung, W. B. (2008). Phenotypic and functional modulation of bone marrow-derived dendritic cells by porcine reproductive and respiratory syndrome virus. Vet. Microbiol. 129, 281-293. doi: 10.1016/j.vetmic.2007.12.002
22. Charerntantanakul, W. (2009). Adjuvants for porcine reproductive and respiratory syndrome virus vaccines. Vet. Immunol. Immunopathol. 129, 1-13. doi: 10. 1016/j.vetimm.2008.12.018
23. Charerntantanakul, W. (2012). Porcine reproductive and respiratory syndrome virus vaccines: Immunogenicity, efficacy and safety aspects. World J. Virol. 1, 23-30. doi: 10.5501/wjv.v1.i1.23
24. Chaudhuri, S., Mckenna, N., Balce, D. R., and Yates, R. M. (2016). Infection of porcine bone marrow-derived macrophages by porcine respiratory and reproductive syndrome virus impairs phagosomal maturation. J. Gen. Virol. 97, 669-679. doi: 10.1099/jgv.0.000384
25. Chen, Z., Lawson, S., Sun, Z., Zhou, X., Guan, X., Christopher-Hennings, J., et al. (2010a). Identification of two auto-cleavage products of nonstructural protein 1 (nsp1) in porcine reproductive and respiratory syndrome virus infected cells: nsp1 function as interferon antagonist. Virology 398, 87-97. doi: 10.1016/j.virol. 2009.11.033
26. Chen, Z., Zhou, X., Lunney, J. K., Lawson, S., Sun, Z., Brown, E., et al. (2010b). Immunodominant epitopes in nsp2 of porcine reproductive and respiratory syndrome virus are dispensable for replication, but play an important role in modulation of the host immune response. J. Gen. Virol. 91, 1047-1057. doi: 10.1099/vir.0.016212-0
27. Chia, M. Y., Hsiao, S. H., Chan, H. T., Do, Y. Y., Huang, P. L., Chang, H. W., et al. (2011). Evaluation of the immunogenicity of a transgenic tobacco plant expressing the recombinant fusion protein of GP5 of porcine reproductive and respiratory syndrome virus and B subunit of Escherichia coli heat-labile enterotoxin in pigs. Vet. Immunol. Immunopathol. 140, 215-225. doi: 10.1016/ j.vetimm.2011.01.002
28. Conzelmann, K. K., Visser, N., Van Woensel, P., and Thiel, H. J. (1993). Molecular characterization of porcine reproductive and respiratory syndrome virus, a member of the arterivirus group. Virology 193, 329-339. doi: 10.1006/viro.1993. 1129
29. Correas, I., Osorio, F. A., Steffen, D., Pattnaik, A. K., and Vu, H. L. (2017). Cross reactivity of immune responses to porcine reproductive and respiratory syndrome virus infection. Vaccine 35, 782-788. doi: 10.1016/j.vaccine.2016. 12.040
30. Costers, S., Vanhee, M., Van Breedam, W., Van Doorsselaere, J., Geldhof, M., and Nauwynck, H. J. (2010). GP4-specific neutralizing antibodies might be a driving force in PRRSV evolution. Virus Res. 154, 104-113. doi: 10.1016/j.virusres.2010. 08.026
31. Cui, J., O'Connell, C. M., Smith, J. D., Pan, Y., Smyth, J. A., Verardi, P. H., et al. (2016). A GP5 Mosaic T-cell vaccine for porcine reproductive and respiratory syndrome virus is immunogenic and confers partial protection to pigs. Vaccine Rep. 6, 77-85. doi: 10.1016/j.vacrep.2016.11.003
32. Das, P. B., Vu, H. L., Dinh, P. X., Cooney, J. L., Kwon, B., Osorio, F. A., et al. (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. doi: 10.1016/j.virol.2010.12.002
33. de Lima, M., Pattnaik, A. K., Flores, E. F., and Osorio, F. A. (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. doi: 10.1016/j.virol.2006.05.036
34. Decker, T., Lew, D. J., Cheng, Y. S., Levy, D. E., and Darnell, J. E Jr. (1989). Interactions of alpha- and gamma-interferon in the transcriptional regulation of the gene encoding a guanylate-binding protein. EMBO J. 8, 2009-2014.
35. Delputte, P. L., Van Breedam, W., Delrue, I., Oetke, C., Crocker, P. R., and Nauwynck, H. J. (2007). Porcine arterivirus attachment to the macrophagespecific receptor sialoadhesin is dependent on the sialic acid-binding activity of the N-terminal immunoglobulin domain of sialoadhesin. J. Virol. 81, 9546-9550. doi: 10.1128/JVI.00569-07
36. Delputte, P. L., Vanderheijden, N., Nauwynck, H. J., and Pensaert, M. B. (2002). Involvement of the matrix protein in attachment of porcine reproductive and respiratory syndrome virus to a heparinlike receptor on porcine alveolar macrophages. J. Virol. 76, 4312-4320. doi: 10.1128/JVI.76.9.4312-4320. 2002
37. Delrue, I., Van Gorp, H., Van Doorsselaere, J., Delputte, P. L., and Nauwynck, H. J. (2010). Susceptible cell lines for the production of porcine reproductive and respiratory syndrome virus by stable transfection of sialoadhesin and CD163. BMC Biotechnol. 10, 48. doi: 10.1186/1472-6750-10-48
38. Diaz, I., Darwich, L., Pappaterra, G., Pujols, J., and Mateu, E. (2006). Different European-type vaccines against porcine reproductive and respiratory syndrome virus have different immunological properties and confer different protection to pigs. Virology 351, 249-259. doi: 10.1016/j.virol.2006.03.046
39. Do, H. Q., Trinh, D. T., Nguyen, T. L., Vu, T. T., Than, D. D., Van Lo, T., et al. (2016). Molecular evolution of type 2 porcine reproductive and respiratory syndrome viruses circulating in Vietnam from 2007 to 2015. BMC Vet. Res. 12:256. doi: 10.1186/s12917-016-0885-3
40. Dokland, T. (2010). The structural biology of PRRSV. Virus Res. 154, 86-97. doi: 10.1016/j.virusres.2010.07.029
41. Dong, S., Yin, Y., Shen, S., Guo, Y., Gao, M., Zhang, W., et al. (2012). Inhibitory effects of recombinant porcine interferon-alpha on high- and low-virulence porcine reproductive and respiratory syndrome viruses. Res. Vet. Sci. 93, 1060- 1065. doi: 10.1016/j.rvsc.2011.12.006
42. Doria-Rose, N. A., Klein, R. M., Manion, M. M., O'dell, S., Phogat, A., Chakrabarti, B., et al. (2009). Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J. Virol. 83, 188-199. doi: 10.1128/JVI.01583-08
43. Du, Y., Du, T., Shi, Y., Zhang, A., Zhang, C., Diao, Y., et al. (2016). Synthetic Tolllike receptor 7 ligand inhibits porcine reproductive and respiratory syndrome virus infection in primary porcine alveolar macrophages. Antiviral Res. 131, 9-18. doi: 10.1016/j.antiviral.2016.04.005
44. Duan, X., Nauwynck, H. J., and Pensaert, M. B. (1997a). Effects of origin and state of differentiation and activation of monocytes/macrophages on their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV). Arch. Virol. 142, 2483-2497.
45. Duan, X., Nauwynck, H. J., and Pensaert, M. B. (1997b). Virus quantification and identification of cellular targets in the lungs and lymphoid tissues of pigs at different time intervals after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV). Vet. Microbiol. 56, 9-19.
46. Dwivedi, V., Manickam, C., Binjawadagi, B., Linhares, D., Murtaugh, M. P., and Renukaradhya, G. J. (2012). Evaluation of immune responses to porcine reproductive and respiratory syndrome virus in pigs during early stage of infection under farm conditions. Virol. J. 9:45. doi: 10.1186/1743-422X-9-45
47. Eroshkin, A. M., Leblanc, A., Weekes, D., Post, K., Li, Z., Rajput, A., et al. (2014). bNAber: database of broadly neutralizing HIV antibodies. Nucleic Acids Res. 42, D1133-D1139. doi: 10.1093/nar/gkt1083
48. Fan, B., Liu, X., Bai, J., Zhang, T., Zhang, Q., and 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. doi: 10.1016/j.virusres.2015. 04.015
49. Fontanella, E., Ma, Z., Zhang, Y., De Castro, A. M., Shen, H., Halbur, P. G., et al. (2017). An interferon inducing porcine reproductive and respiratory syndrome virus vaccine candidate elicits protection against challenge with the heterologous virulent type 2 strain VR-2385 in pigs. Vaccine 35, 125-131. doi: 10.1016/j.vaccine.2016.11.020
50. Forsberg, R. (2005). Divergence time of porcine reproductive and respiratory syndrome virus subtypes. Mol. Biol. Evol. 22, 2131-2134. doi: 10.1093/molbev/ msi208
51. Forsberg, R., Storgaard, T., Nielsen, H. S., Oleksiewicz, M. B., Cordioli, P., Sala, G., et al. (2002). The genetic diversity of European type PRRSV is similar to that of the North American type but is geographically skewed within Europe. Virology 299, 38-47. doi: 10.1006/viro.2002.1450
52. Gagnon, C. A., Lachapelle, G., Langelier, Y., Massie, B., and Dea, S. (2003). Adenoviral-expressed GP5 of porcine respiratory and reproductive syndrome virus differs in its cellular maturation from the authentic viral protein but maintains known biological functions. Arch. Virol. 148, 951-972. doi: 10.1007/ s00705-002-0943-y
53. Gao, J., Xiao, S., Xiao, Y., Wang, X., Zhang, C., Zhao, Q., et al. (2016). MYH9 is an essential factor for porcine reproductive and respiratory syndrome virus infection. Sci. Rep. 6:25120. doi: 10.1038/srep25120
54. Gonzalez-Navajas, J. M., Lee, J., David, M., and Raz, E. (2012). Immunomodulatory functions of type I interferons. Nat. Rev. Immunol. 12, 125-135. doi: 10.1038/ nri3133
55. Goyal, S. M. (1993). Porcine reproductive and respiratory syndrome. J. Vet. Diagn. Invest. 5, 656-664. doi: 10.1177/104063879300500435
56. Guo, B., Lager, K. M., Henningson, J. N., Miller, L. C., Schlink, S. N., Kappes, M. A., et al. (2013). Experimental infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. Virology 435, 372-384. doi: 10.1016/j.virol.2012.09.013
57. Guo, L., Niu, J., Yu, H., Gu, W., Li, R., Luo, X., et al. (2014). Modulation of CD163 expression by metalloprotease ADAM17 regulates porcine reproductive and respiratory syndrome virus entry. J. Virol. 88, 10448-10458. doi: 10.1128/JVI. 01117-14
58. Han, J., Wang, Y., and Faaberg, K. S. (2006). Complete genome analysis of RFLP 184 isolates of porcine reproductive and respiratory syndrome virus. Virus Res. 122, 175-182. doi: 10.1016/j.virusres.2006.06.003
59. Hanada, K., Suzuki, Y., Nakane, T., Hirose, O., and Gojobori, T. (2005). The origin and evolution of porcine reproductive and respiratory syndrome viruses. Mol. Biol. Evol. 22, 1024-1031. doi: 10.1093/molbev/msi089
60. Huang, C., Zhang, Q., Guo, X. K., Yu, Z. B., Xu, A. T., Tang, J., et al. (2014). Porcine reproductive and respiratory syndrome virus nonstructural protein 4 antagonizes beta interferon expression by targeting the NFkappaB essential modulator. J. Virol. 88, 10934-10945. doi: 10.1128/JVI. 01396-14
61. Huang, Y. W., Dryman, B. A., Li, W., and Meng, X. J. (2009). Porcine DCSIGN: molecular cloning, gene structure, tissue distribution and binding characteristics. Dev. Comp. Immunol. 33, 464-480. doi: 10.1016/j.dci.2008. 09.010
62. Jiang, W., Jiang, P., Wang, X., Li, Y., and Du, Y. (2007). Influence of porcine reproductive and respiratory syndrome virus GP5 glycoprotein N-linked glycans on immune responses in mice. Virus Gen. 35, 663-671. doi: 10.1007/ s11262-007-0131-y
63. Jiang, W., Jiang, P., Wang, X., Li, Y., and Du, Y. (2008). Enhanced immune responses of mice inoculated recombinant adenoviruses expressing GP5 by fusion with GP3 and/or GP4 of PRRS virus. Virus Res. 136, 50-57. doi: 10.1016/ j.virusres.2008.04.016
64. Jiang, Z., Zhou, E. M., Ameri-Mahabadi, M., Zimmerman, J. J., and Platt, K. B. (2003). Identification and characterization of auto-anti-idiotypic antibodies specific for antibodies against porcine reproductive and respiratory syndrome virus envelope glycoprotein (GP5). Vet. Immunol. Immunopathol. 92, 125-135. doi: 10.1016/S0165-2427(03)00022-9
65. Kappes, M. A., and Faaberg, K. S. (2015). PRRSV structure, replication and recombination: Origin of phenotype and genotype diversity. Virology 479-480, 475-486. doi: 10.1016/j.virol.2015.02.012
66. Karniychuk, U. U., Geldhof, M., Vanhee, M., Van Doorsselaere, J., Saveleva, T. A., and Nauwynck, H. J. (2010). Pathogenesis and antigenic characterization of a new East European subtype 3 porcine reproductive and respiratory syndrome virus isolate. BMC Vet. Res. 6:30. doi: 10.1186/1746-6148-6-30
67. Katze, M. G., He, Y., and Gale, M. Jr. (2002). Viruses and interferon: a fight for supremacy. Nat. Rev. Immunol. 2, 675-687. doi: 10.1038/nri888
68. Kim, H., Kim, H. K., Jung, J. H., Choi, Y. J., Kim, J., Um, C. G., et al. (2011). The assessment of efficacy of porcine reproductive respiratory syndrome virus inactivated vaccine based on the viral quantity and inactivation methods. Virol. J. 8:323. doi: 10.1186/1743-422X-8-323
69. Kim, J. K., Fahad, A. M., Shanmukhappa, K., and Kapil, S. (2006). Defining the cellular target(s) of porcine reproductive and respiratory syndrome virus blocking monoclonal antibody 7G10. J. Virol. 80, 689-696. doi: 10.1128/JVI.80. 2.689-696.2006
70. Kim, W. I., Kim, J. J., Cha, S. H., Wu, W. H., Cooper, V., Evans, R., et al. (2013). Significance of genetic variation of PRRSV ORF5 in virus neutralization and molecular determinants corresponding to cross neutralization among PRRS viruses. Vet. Microbiol. 162, 10-22. doi: 10.1016/j.vetmic.2012.08.005
71. Kim, W. I., and Yoon, K. J. (2008). Molecular assessment of the role of envelopeassociated structural proteins in cross neutralization among different PRRS viruses. Virus Genes 37, 380-391. doi: 10.1007/s11262-008-0278-1
72. Kuhn, J. H., Lauck, M., Bailey, A. L., Shchetinin, A. M., Vishnevskaya, T. V., Bao, Y., et al. (2016). Reorganization and expansion of the nidoviral family Arteriviridae. Arch. Virol. 161, 755-768. doi: 10.1007/s00705-015-2672-z
73. Labarque, G. G., Nauwynck, H. J., Van Reeth, K., and Pensaert, M. B. (2000). Effect of cellular changes and onset of humoral immunity on the replication of porcine reproductive and respiratory syndrome virus in the lungs of pigs. J. Gen. Virol. 81, 1327-1334. doi: 10.1099/0022-1317-81-5-1327
74. Lee, C., Bachand, A., Murtaugh, M. P., and Yoo, D. (2004). Differential host cell gene expression regulated by the porcine reproductive and respiratory syndrome virus GP4 and GP5 glycoproteins. Vet. Immunol. Immunopathol. 102, 189-198. doi: 10.1016/j.vetimm.2004.09.020
75. Leng, C. L., An, T. Q., Chen, J. Z., Gong, D. Q., Peng, J. M., Yang, Y. Q., et al. (2012). Highly pathogenic porcine reproductive and respiratory syndrome virus GP5 B antigenic region is not a neutralizing antigenic region. Vet. Microbiol. 159, 273-281. doi: 10.1016/j.vetmic.2012.06.018
76. Leng, X., Li, Z., Xia, M., Li, X., Wang, F., Wang, W., et al. (2012). Mutations in the genome of the highly pathogenic porcine reproductive and respiratory syndrome virus potentially related to attenuation. Vet. Microbiol. 157, 50-60. doi: 10.1016/j.vetmic.2011.12.012
77. Lew, D. J., Decker, T., and Darnell, J. E. Jr. (1989). Alpha interferon and gamma interferon stimulate transcription of a single gene through different signal transduction pathways. Mol. Cell. Biol. 9, 5404-5411. doi: 10.1128/MCB.9.12. 5404
78. Li, C., Zhuang, J., Wang, J., Han, L., Sun, Z., Xiao, Y., et al. (2016). Outbreak investigation of NADC30-Like PRRSV in South-East China. Transbound Emerg. Dis. 63, 474-479. doi: 10.1111/tbed.12530
79. Li, H., Zheng, Z., Zhou, P., Zhang, B., Shi, Z., Hu, Q., et al. (2010). The cysteine protease domain of porcine reproductive and respiratory syndrome virus nonstructural protein 2 antagonizes interferon regulatory factor 3 activation. J. Gen. Virol. 91, 2947-2958. doi: 10.1099/vir.0.025205-0
80. Li, J., and Murtaugh, M. P. (2012). Dissociation of porcine reproductive and respiratory syndrome virus neutralization from antibodies specific to major envelope protein surface epitopes. Virology 433, 367-376. doi: 10.1016/j.virol. 2012.08.026
81. Liu, Y., Shi, W., Zhou, E., Wang, S., Hu, S., Cai, X., et al. (2010). Dynamic changes in inflammatory cytokines in pigs infected with highly pathogenic porcine reproductive and respiratory syndrome virus. Clin. Vaccine Immunol. 17, 1439-1445. doi: 10.1128/CVI.00517-09
82. Liu, Y. J. (2005). IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 23, 275-306. doi: 10.1146/annurev.immunol.23.021704.115633
83. Lopez, O. J., and Osorio, F. A. (2004). Role of neutralizing antibodies in PRRSV protective immunity. Vet. Immunol. Immunopathol. 102, 155-163. doi: 10. 1016/j.vetimm.2004.09.005
84. Lunney, J. K., Fang, Y., Ladinig, A., Chen, N., Li, Y., Rowland, B., et al. (2016). Porcine reproductive and respiratory syndrome virus (PRRSV): pathogenesis and interaction with the immune system. Annu. Rev. Anim. Biosci. 4, 129-154. doi: 10.1146/annurev-animal-022114-111025
85. Luo, Y., Li, S., Sun, Y., and Qiu, H. J. (2014). Classical swine fever in China: a minireview. Vet. Microbiol. 172, 1-6. doi: 10.1016/j.vetmic.2014.04.004
86. Ma, Z., Yu, Y., Xiao, Y., Opriessnig, T., Wang, R., Yang, L., et al. (2016). Sustaining interferon induction by a high-passage atypical porcine reproductive and respiratory syndrome virus strain. Sci. Rep. 6:36312. doi: 10.1038/srep36312
87. Ma, Z., Yu, Y., Xiao, Y., Opriessnig, T., Wang, R., Yang, L., et al. (2017). The middle half genome of interferon-inducing porcine reproductive and respiratory syndrome virus strain A2MC2 is essential for interferon induction. J. Gen. Virol. doi: 10.1099/jgv.0.000819 [Epub ahead of print].
88. Madsen, K. G., Hansen, C. M., Madsen, E. S., Strandbygaard, B., Botner, A., and Sorensen, K. J. (1998). Sequence analysis of porcine reproductive and respiratory syndrome virus of the American type collected from Danish swine herds. Arch. Virol. 143, 1683-1700. doi: 10.1007/s007050050409
89. Mardassi, H., Massie, B., and 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. doi: 10.1006/viro.1996.0356
90. Mardassi, H., Mounir, S., and Dea, S. (1994). Identification of major differences in the nucleocapsid protein genes of a Quebec strain and European strains of porcine reproductive and respiratory syndrome virus. J. Gen. Virol. 75 ( Pt 3), 681-685. doi: 10.1099/0022-1317-75-3-681
91. Mardassi, H., Mounir, S., and Dea, S. (1995). Molecular analysis of the ORFs 3 to 7 of porcine reproductive and respiratory syndrome virus, Quebec reference strain. Arch. Virol. 140, 1405-1418. doi: 10.1007/BF01322667
92. Martinez-Lobo, F. J., Diez-Fuertes, F., Simarro, I., Castro, J. M., and Prieto, C. (2011). Porcine Reproductive and Respiratory Syndrome Virus isolates differ in their susceptibility to neutralization. Vaccine 29, 6928-6940. doi: 10.1016/j. vaccine.2011.07.076
93. Mascola, J. R., and Haynes, B. F. (2013). HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol. Rev. 254, 225-244. doi: 10.1111/ imr.12075
94. Meng, X. J., Paul, P. S., Halbur, P. G., and Lum, M. A. (1996). Characterization of a high-virulence US isolate of porcine reproductive and respiratory syndrome virus in a continuous cell line, ATCC CRL11171. J. Vet. Diagn. Invest. 8, 374-381. doi: 10.1177/104063879600800317
95. Mengeling, W. L., Lager, K. M., and Vorwald, A. C. (1998). Clinical consequences of exposing pregnant gilts to strains of porcine reproductive and respiratory syndrome (PRRS) virus isolated from field cases of "atypical" PRRS. Am. J. Vet. Res. 59, 1540-1544.
96. Mengeling, W. L., Lager, K. M., Vorwald, A. C., and Koehler, K. J. (2003). Strain specificity of the immune response of pigs following vaccination with various strains of porcine reproductive and respiratory syndrome virus. Vet. Microbiol. 93, 13-24. doi: 10.1016/S0378-1135(02)00427-3
97. Morgan, S. B., Frossard, J. P., Pallares, F. J., Gough, J., Stadejek, T., Graham, S. P., et al. (2014). Pathology and virus distribution in the lung and lymphoid tissues of pigs experimentally inoculated with three distinct type 1 PRRS virus isolates of varying pathogenicity. Transbound. Emerg. Dis. 63, 285-295. doi: 10.1111/tbed.12272
98. Morgan, S. B., Graham, S. P., Salguero, F. J., Sanchez Cordon, P. J., Mokhtar, H., Rebel, J. M., et al. (2013). Increased pathogenicity of European porcine reproductive and respiratory syndrome virus is associated with enhanced adaptive responses and viral clearance. Vet.Microbiol. 163, 13-22. doi: 10.1016/ j.vetmic.2012.11.024
99. Murtaugh, M. P., Stadejek, T., Abrahante, J. E., Lam, T. T., and Leung, F. C. (2010). The ever-expanding diversity of porcine reproductive and respiratory syndrome virus. Virus Res. 154, 18-30. doi: 10.1016/j.virusres.2010.08.015
100. Nan, Y., Nan, G., and Zhang, Y. J. (2014). Interferon induction by RNA viruses and antagonism by viral pathogens. Viruses 6, 4999-5027. doi: 10.3390/v6124999
101. Nan, Y., Wang, R., Shen, M., Faaberg, K. S., Samal, S. K., and Zhang, Y. J. (2012). Induction of type I interferons by a novel porcine reproductive and respiratory syndrome virus isolate. Virology 432, 261-270. doi: 10.1016/j.virol.2012.05.015
102. Ni, Y. Y., Huang, Y. W., Cao, D., Opriessnig, T., and Meng, X. J. (2011). Establishment of a DNA-launched infectious clone for a highly pneumovirulent strain of type 2 porcine reproductive and respiratory syndrome virus: identification and in vitro and in vivo characterization of a large spontaneous deletion in the nsp2 region. Virus Res. 160, 264-273. doi: 10.1016/j.virusres. 2011.06.027
103. Nilubol, D., Platt, K. B., Halbur, P. G., Torremorell, M., and Harris, D. L. (2004). The effect of a killed porcine reproductive and respiratory syndrome virus (PRRSV) vaccine treatment on virus shedding in previously PRRSV infected pigs. Vet. Microbiol. 102, 11-18. doi: 10.1016/j.vetmic.2004.05.006
104. Obdulio, G.-N., Gae, A., Julie, R., Nicolas, R., and Artur, S. (2015). Potent Interferon-alpha Production by Plasmacytoid Dendritic Cells Co-Cultured with Macrophages Pre-Infected with Genotype 1 or Genotype 2 Highly Pathogenic PRRSV [Online]. PRRS.com. Available at: https://www.prrs.com/en/publi cations/abstracts/potent-interferon-alpha-production-plasmacytoid-dendriticcells- cultured-with-macrophages-pre-infected-with-genotype-1-genotype-2- highly-pathogenic-po/ [accessed March 6, 2015].
105. Opriessnig, T., Halbur, P. G., Yoon, K. J., Pogranichniy, R. M., Harmon, K. M., Evans, R., et al. (2002). Comparison of molecular and biological characteristics of a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine (ingelvac PRRS MLV), the parent strain of the vaccine (ATCC VR2332), ATCC VR2385, and two recent field isolates of PRRSV. J. Virol. 76, 11837-11844. doi: 10.1128/JVI.76.23.11837-11844.2002
106. Ostrowski, M., Galeota, J. A., Jar, A. M., Platt, K. B., Osorio, F. A., and Lopez, O. J. (2002). Identification of neutralizing and nonneutralizing epitopes in the porcine reproductive and respiratory syndrome virus GP5 ectodomain. J. Virol. 76, 4241-4250. doi: 10.1128/JVI.76.9.4241-4250.2002
107. Pan, X. (2014). Single cell analysis: from technology to biology and medicine. Single Cell Biol. 3:106. Papatsiros, V. G., Alexopoulos, C., Kritas, S. K., Koptopoulos, G., Nauwynck, H. J.
108. Papatsiros, V. G., Alexopoulos, C., Kritas, S. K., Koptopoulos, G., Nauwynck, H. J., Pensaert, M. B., et al. (2006). Long-term administration of a commercial porcine reproductive and respiratory syndrome virus (PRRSV)-inactivated vaccine in PRRSV-endemically infected sows. J. Vet. Med. B Infect. Dis. Vet. Public Health 53, 266-272. doi: 10.1111/j.1439-0450.2006.00965.x
109. Patel, D., Nan, Y., Shen, M., Ritthipichai, K., Zhu, X., and Zhang, Y. J. (2010). Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear translocation. J. Virol. 84, 11045- 11055. doi: 10.1128/JVI.00655-10
110. Pestka, S. (2007). The interferons: 50 years after their discovery, there is much more to learn. J. Biol. Chem. 282, 20047-20051. doi: 10.1074/jbc.R7000 04200
111. Pestka, S., Krause, C. D., and Walter, M. R. (2004). Interferons, interferon-like cytokines, and their receptors. Immunol. Rev. 202, 8-32. doi: 10.1111/j.0105- 2896.2004.00204.x
112. Pineyro, P. E., Subramaniam, S., Kenney, S. P., Heffron, C. L., Gimenez-Lirola, L. G., and Meng, X. J. (2016). Modulation of proinflammatory cytokines in monocyte-derived dendritic cells by porcine reproductive and respiratory syndrome virus through interaction with the porcine intercellular-adhesionmolecule- 3-grabbing nonintegrin. Viral Immunol. 29, 546-556. doi: 10.1089/ vim.2016.0104
113. Piras, F., Bollard, S., Laval, F., Joisel, F., Reynaud, G., Charreyre, C., et al. (2005). Porcine reproductive and respiratory syndrome (PRRS) virus-specific interferon-gammaC T-cell responses after PRRS virus infection or vaccination with an inactivated PRRS vaccine. Viral Immunol. 18, 381-389. doi: 10.1089/ vim.2005.18.381
114. Pirzadeh, B., and 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. doi: 10.1099/0022-1317-78-8- 1867
115. Plagemann, P. G., Rowland, R. R., and Faaberg, K. S. (2002). The primary neutralization epitope of porcine respiratory and reproductive syndrome virus strain VR-2332 is located in the middle of the GP5 ectodomain. Arch. Virol. 147, 2327-2347. doi: 10.1007/s00705-002-0887-2
116. Plana Duran, J., Climent, I., Sarraseca, J., Urniza, A., Cortes, E., Vela, C., et al. (1997). Baculovirus expression of proteins of porcine reproductive and respiratory syndrome virus strain Olot/91. Involvement of ORF3 and ORF5 proteins in protection. Virus Genes 14, 19-29. doi: 10.1023/A:1007931322271
117. Rajkhowa, T. K., Jagan Mohanarao, G., Gogoi, A., Hauhnar, L., and Isaac, L. (2015). Porcine reproductive and respiratory syndrome virus (PRRSV) from the first outbreak of India shows close relationship with the highly pathogenic variant of China. Vet. Q. 35, 186-193. doi: 10.1080/01652176.2015.1066043
118. Renukaradhya, G. J., Meng, X. J., Calvert, J. G., Roof, M., and Lager, K. M. (2015a). Inactivated and subunit vaccines against porcine reproductive and respiratory syndrome: current status and future direction. Vaccine 33, 3065-3072. doi: 10.1016/j.vaccine.2015.04.102
119. Renukaradhya, G. J., Meng, X. J., Calvert, J. G., Roof, M., and Lager, K. M. (2015b). Live porcine reproductive and respiratory syndrome virus vaccines: current status and future direction. Vaccine 33, 4069-4080. doi: 10.1016/j.vaccine.2015. 06.092
120. Robinson, S. R., Li, J., Nelson, E. A., and Murtaugh, M. P. (2015). Broadly neutralizing antibodies against the rapidly evolving porcine reproductive and respiratory syndrome virus. Virus Res. 203, 56-65. doi: 10.1016/j.virusres.2015. 03.016
121. Roca, M., Gimeno, M., Bruguera, S., Segales, J., Diaz, I., Galindo-Cardiel, I. J., et al. (2012). Effects of challenge with a virulent genotype II strain of porcine reproductive and respiratory syndrome virus on piglets vaccinated with an attenuated genotype I strain vaccine. Vet. J. 193, 92-96. doi: 10.1016/j.tvjl.2011. 11.019
122. Rock, D. L. (2007). Report: Colloquium on Prospects for Development of an Effective PRRS Virus Vaccine. Perry, IA: American Association of Swine Veterinarians.
123. Rowland, R. R., Lunney, J., and Dekkers, J. (2012). Control of porcine reproductive and respiratory syndrome (PRRS) through genetic improvements in disease resistance and tolerance. Front. Genet. 3:260. doi: 10.3389/fgene.2012.00260
124. Sagong, M., and Lee, C. (2011). Porcine reproductive and respiratory syndrome virus nucleocapsid protein modulates interferon-beta production by inhibiting IRF3 activation in immortalized porcine alveolar macrophages. Arch. Virol. 156, 2187-2195. doi: 10.1007/s00705-011-1116-7
125. Scheid, J. F., Mouquet, H., Feldhahn, N., Seaman, M. S., Velinzon, K., Pietzsch, J., et al. (2009a). Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458, 636-640. doi: 10.1038/ nature07930
126. Scheid, J. F., Mouquet, H., Feldhahn, N., Walker, B. D., Pereyra, F., Cutrell, E., et al. (2009b). A method for identification of HIV gp140 binding memory B cells in human blood. J. Immunol. Methods 343, 65-67. doi: 10.1016/j.jim.2008.11.012
127. Schindler, C., Shuai, K., Prezioso, V. R., and Darnell, J. E. Jr. (1992). Interferondependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 257, 809-813. doi: 10.1126/science.1496401
128. Scortti, M., Prieto, C., Alvarez, E., Simarro, I., and Castro, J. M. (2007). Failure of an inactivated vaccine against porcine reproductive and respiratory syndrome to protect gilts against a heterologous challenge with PRRSV. Vet. Rec. 161, 809-813.
129. Shen, G., Jin, N., Ma, M., Jin, K., Zheng, M., Zhuang, T., et al. (2007). Immune responses of pigs inoculated with a recombinant fowlpox virus coexpressing GP5/GP3 of porcine reproductive and respiratory syndrome virus and swine IL-18. Vaccine 25, 4193-4202. doi: 10.1016/j.vaccine.2007.03.010
130. Shi, C., Liu, Y., Ding, Y., Zhang, Y., and Zhang, J. (2015). PRRSV receptors and their roles in virus infection. Arch. Microbiol. 197, 503-512. doi: 10.1007/ s00203-015-1088-1
131. Shi, M., Lam, T. T., Hon, C. C., Hui, R. K., Faaberg, K. S., Wennblom, T., et al. (2010). Molecular epidemiology of PRRSV: a phylogenetic perspective. Virus Res. 154, 7-17. doi: 10.1016/j.virusres.2010.08.014
132. Shi, X., Wang, L., Li, X., Zhang, G., Guo, J., Zhao, D., et al. (2011). Endoribonuclease activities of porcine reproductive and respiratory syndrome virus nsp11 was essential for nsp11 to inhibit IFN-beta induction. Mol. Immunol. 48, 1568-1572. doi: 10.1016/j.molimm.2011.03.004
133. Siegal, F. P., Kadowaki, N., Shodell, M., Fitzgerald-Bocarsly, P. A., Shah, K., Ho, S., et al. (1999). The nature of the principal type 1 interferon-producing cells in human blood. Science 284, 1835-1837. doi: 10.1126/science.284.5421.1835
134. Simek, M. D., Rida, W., Priddy, F. H., Pung, P., Carrow, E., Laufer, D. S., et al. (2009). Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a highthroughput neutralization assay together with an analytical selection algorithm. J. Virol. 83, 7337-7348. doi: 10.1128/JVI.00110-09
135. Sirisereewan, C., Nedumpun, T., Kesdangsakonwut, S., Woonwong, Y., Kedkovid, R., Arunorat, J., et al. (2017). Positive immunomodulatory effects of heterologous DNA vaccine- modified live vaccine, prime-boost immunization, against the highly-pathogenic PRRSV infection. Vet. Immunol. Immunopathol. 183, 7-15. doi: 10.1016/j.vetimm.2016.11.002
136. Snijder, E. J., and Meulenberg, J. J. (1998). The molecular biology of arteriviruses. J. Gen. Virol. 79(Pt 5), 961-979. doi: 10.1099/0022-1317-79-5-961
137. Stadejek, T., Stankevicius, A., Murtaugh, M. P., and Oleksiewicz, M. B. (2013). Molecular evolution of PRRSV in Europe: current state of play. Vet. Microbiol. 165, 21-28. doi: 10.1016/j.vetmic.2013.02.029
138. Sun, H., Pattnaik, A. K., Osorio, F. A., and Vu, H. L. (2016). Identification of viral genes associated with the interferon-inducing phenotype of a synthetic porcine reproductive and respiratory syndrome virus strain. Virology 499, 313-321. doi: 10.1016/j.virol.2016.09.018
139. Sun, Z., Chen, Z., Lawson, S. R., and Fang, Y. (2010). The cysteine protease domain of porcine reproductive and respiratory syndrome virus nonstructural protein 2 possesses deubiquitinating and interferon antagonism functions. J. Virol. 84, 7832-7846. doi: 10.1128/JVI.00217-10
140. Sur, J. H., Cooper, V. L., Galeota, J. A., Hesse, R. A., Doster, A. R., and Osorio, F. A. (1996). In vivo detection of porcine reproductive and respiratory syndrome virus RNA by in situ hybridization at different times postinfection. J. Clin. Microbiol. 34, 2280-2286.
141. Thaa, B., Sinhadri, B. C., Tielesch, C., Krause, E., and Veit, M. (2013). Signal peptide cleavage from GP5 of PRRSV: a minor fraction of molecules retains the decoy epitope, a presumed molecular cause for viral persistence. PLoS ONE 8:e65548. doi: 10.1371/journal.pone.0065548
142. Tian, D., Cao, D., Lynn Heffron, C., Yugo, D. M., Rogers, A. J., Overend, C., et al. (2017). Enhancing heterologous protection in pigs vaccinated with chimeric porcine reproductive and respiratory syndrome virus containing the full-length sequences of shuffled structural genes of multiple heterologous strains. Vaccine 35, 2427-2434. doi: 10.1016/j.vaccine.2017.03.046
143. Tian, K., Yu, X., Zhao, T., Feng, Y., Cao, Z., Wang, C., et al. (2007). Emergence of fatal PRRSV variants: unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark. PLoS ONE 2:e526. doi: 10.1371/ journal.pone.0000526
144. Tiller, T., Meffre, E., Yurasov, S., Tsuiji, M., Nussenzweig, M. C., and Wardemann, H. (2008). Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J. Immunol. Methods 329, 112-124. doi: 10.1016/j.jim.2007.09.017
145. Trible, B. R., Popescu, L. N., Monday, N., Calvert, J. G., and Rowland, R. R. (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. doi: 10.1128/JVI. 03287-14
146. Trkola, A., Pomales, A. B., Yuan, H., Korber, B., Maddon, P. J., Allaway, G. P., et al. (1995). Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG. J. Virol. 69, 6609-6617.
147. Trus, I., Bonckaert, C., Van Der Meulen, K., and Nauwynck, H. J. (2014). Efficacy of an attenuated European subtype 1 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in pigs upon challenge with the East European subtype 3 PRRSV strain Lena. Vaccine 32, 2995-3003. doi: 10.1016/j.vaccine. 2014.03.077
148. Uze, G., Schreiber, G., Piehler, J., and Pellegrini, S. (2007). The receptor of the type I interferon family. Curr. Top. Microbiol. Immunol. 316, 71-95. doi: 10.1007/ 978-3-540-71329-6_5
149. Valente, G., Ozmen, L., Novelli, F., Geuna, M., Palestro, G., Forni, G., et al. (1992). Distribution of interferon-gamma receptor in human tissues. Eur. J. Immunol. 22, 2403-2412. doi: 10.1002/eji.1830220933
150. Van Breedam, W., Costers, S., Vanhee, M., Gagnon, C. A., Rodriguez-Gomez, I. M., Geldhof, M., et al. (2011). Porcine reproductive and respiratory syndrome virus (PRRSV)-specific mAbs: supporting diagnostics and providing new insights into the antigenic properties of the virus. Vet. Immunol. Immunopathol. 141, 246-257. doi: 10.1016/j.vetimm.2011.03.008
151. Van Breedam, W., Delputte, P. L., Van Gorp, H., Misinzo, G., Vanderheijden, N., Duan, X., et al. (2010). Porcine reproductive and respiratory syndrome virus entry into the porcine macrophage. J. Gen. Virol. 91, 1659-1667. doi: 10.1099/ vir.0.020503-0
152. van Woensel, P. A., Liefkens, K., and Demaret, S. (1998). Effect on viraemia of an American and a European serotype PRRSV vaccine after challenge with European wild-type strains of the virus. Vet. Rec. 142, 510-512. doi: 10.1136/ vr.142.19.510
153. Vanhee, M., Costers, S., Van Breedam, W., Geldhof, M. F., Van Doorsselaere, J., and Nauwynck, H. J. (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. doi: 10.1089/vim.2010.0025
154. Vanhee, M., Van Breedam, W., Costers, S., Geldhof, M., Noppe, Y., and 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. doi: 10.1016/j.vaccine.2011.04.071
155. Vu, H. L., Ma, F., Laegreid, W. W., Pattnaik, A. K., Steffen, D., Doster, A. R., et al. (2015). A synthetic porcine reproductive and respiratory syndrome virus strain confers unprecedented levels of heterologous protection. J. Virol. 89, 12070-12083. doi: 10.1128/JVI.01657-15
156. Wang, C., Wu, B., Amer, S., Luo, J., Zhang, H., Guo, Y., et al. (2010). Phylogenetic analysis and molecular characteristics of seven variant Chinese field isolates of PRRSV. BMC Microbiol. 10:146. doi: 10.1186/1471-2180-10-146
157. Wang, G., Li, L., Yu, Y., Tu, Y., Tong, J., Zhang, C., et al. (2016). Highly pathogenic porcine reproductive and respiratory syndrome virus infection and induction of apoptosis in bone marrow cells of infected piglets. J. Gen. Virol. 97, 1356-1361. doi: 10.1099/jgv.0.000454
158. Wang, R., Nan, Y., Yu, Y., Yang, Z., and Zhang, Y. J. (2013a). Variable interference with interferon signal transduction by different strains of porcine reproductive and respiratory syndrome virus. Vet. Microbiol. 166, 493-503. doi: 10.1016/j. vetmic.2013.07.022
159. Wang, R., Nan, Y., Yu, Y., and Zhang, Y. J. (2013b). Porcine reproductive and respiratory syndrome virus Nsp1beta inhibits interferon-activated JAK/STAT signal transduction by inducing karyopherin-alpha1 degradation. J. Virol. 87, 5219-5228. doi: 10.1128/JVI.02643-12
160. Wang, R., Xiao, Y., Opriessnig, T., Ding, Y., Yu, Y., Nan, Y., et al. (2013c). Enhancing neutralizing antibody production by an interferon-inducing porcine reproductive and respiratory syndrome virus strain. Vaccine 31, 5537-5543. doi: 10.1016/j.vaccine.2013.09.023
161. Wang, R., and Zhang, Y. J. (2014). Antagonizing interferon-mediated immune response by porcine reproductive and respiratory syndrome virus. Biomed Res. Int 2014:315470. doi: 10.1155/2014/315470
162. Wang, X., Wei, R., Li, Q., Liu, H., Huang, B., Gao, J., et al. (2013d). PK-15 cells transfected with porcine CD163 by PiggyBac transposon system are susceptible to porcine reproductive and respiratory syndrome virus. J. Virol. Methods 193, 383-390. doi: 10.1016/j.jviromet.2013.06.035
163. Weiland, E., Wieczorek-Krohmer, M., Kohl, D., Conzelmann, K. K., and Weiland, F. (1999). Monoclonal antibodies to the GP5 of porcine reproductive and respiratory syndrome virus are more effective in virus neutralization than monoclonal antibodies to the GP4. Vet. Microbiol. 66, 171-186. doi: 10.1016/ S0378-1135(99)00006-1
164. Welch, S. K., Jolie, R., Pearce, D. S., Koertje, W. D., Fuog, E., Shields, S. L., et al. (2004). Construction and evaluation of genetically engineered replication-defective porcine reproductive and respiratory syndrome virus vaccine candidates. Vet. Immunol. Immunopathol. 102, 277-290. doi: 10.1016/ j.vetimm.2004.09.022
165. Wenhui, L., Zhongyan, W., Guanqun, Z., Zhili, L., Jingyun, M., Qingmei, X., et al. (2012). Complete genome sequence of a novel variant porcine reproductive and respiratory syndrome virus (PRRSV) strain: evidence for recombination between vaccine and wild-type PRRSV strains. J. Virol. 86, 9543. doi: 10.1128/ JVI.01341-12
166. Wensvoort, G., Terpstra, C., Pol, J. M., Ter Laak, E. A., Bloemraad, M., De Kluyver, E. P., et al. (1991). Mystery swine disease in The Netherlands: the isolation of Lelystad virus. Vet. Q. 13, 121-130. doi: 10.1080/01652176.1991.9694296
167. Wieringa, R., De Vries, A. A., Van Der Meulen, J., Godeke, G. J., Onderwater, J. J., Van Tol, H., et al. (2004). Structural protein requirements in equine arteritis virus assembly. J. Virol. 78, 13019-13027. doi: 10.1128/JVI.78.23.13019-13027. 2004
168. Wissink, E. H., Kroese, M. V., Van Wijk, H. A., Rijsewijk, F. A., Meulenberg, J. J., and Rottier, P. J. (2005). Envelope protein requirements for the assembly of infectious virions of porcine reproductive and respiratory syndrome virus. J. Virol. 79, 12495-12506. doi: 10.1128/JVI.79.19.12495-12506.2005
169. Wu, J., Peng, X., Zhou, A., Qiao, M., Wu, H., Xiao, H., et al. (2014). MiR-506 inhibits PRRSV replication in MARC-145 cells via CD151. Mol. Cell. Biochem. 394, 275-281. doi: 10.1007/s11010-014-2103-6
170. Xiao, Z., Batista, L., Dee, S., Halbur, P., and Murtaugh, M. P. (2004). The level of virus-specific T-cell and macrophage recruitment in porcine reproductive and respiratory syndrome virus infection in pigs is independent of virus load. J. Virol. 78, 5923-5933. doi: 10.1128/JVI.78.11.5923-5933.2004
171. Yang, L., Frey, M. L., Yoon, K. J., Zimmerman, J. J., and Platt, K. B. (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. doi: 10.1007/ s007050070079
172. Yang, L., Wang, R., Ma, Z., Xiao, Y., Nan, Y., Wang, Y., et al. (2017). Porcine reproductive and respiratory syndrome virus antagonizes JAK/STAT3 signaling via nsp5, which induces STAT3 degradation. J. Virol. 91:e02087-16. doi: 10. 1128/JVI.02087-16
173. Yoon, K.-J. (1995). Antibody Dependent Enhancement and its Potential as a Contributing Factor to the Pathogenesis of Porcine Reproductive and Respiratory Syndrome Virus Infection. Doctoral dissertion, Iowa State University, Ames, IA.
174. Yoon, K. J., Wu, L. L., Zimmerman, J. J., Hill, H. T., and Platt, K. B. (1996). Antibody-dependent enhancement (ADE) of porcine reproductive and respiratory syndrome virus (PRRSV) infection in pigs. Viral Immunol. 9, 51-63. doi: 10.1089/vim.1996.9.51
175. Yoon, K. J., Wu, L. L., Zimmerman, J. J., and Platt, K. B. (1997). Field isolates of porcine reproductive and respiratory syndrome virus (PRRSV) vary in their susceptibility to antibody dependent enhancement (ADE) of infection. Vet. Microbiol. 55, 277-287. doi: 10.1016/S0378-1135(96)01338-7
176. Zhang, L., Bai, J., Liu, J., Wang, X., Li, Y., and Jiang, P. (2013). Toll-like receptor ligands enhance the protective effects of vaccination against porcine reproductive and respiratory syndrome virus in swine. Vet. Microbiol. 164, 253-260. doi: 10.1016/j.vetmic.2013.02.016
177. Zhang, Q., and Yoo, D. (2015). PRRS virus receptors and their role for pathogenesis. Vet. Microbiol. 177, 229-241. doi: 10.1016/j.vetmic.2015.04.002
178. Zhang, Y., Sharma, R. D., and Paul, P. S. (1998). Monoclonal antibodies against conformationally dependent epitopes on porcine reproductive and respiratory syndrome virus. Vet. Microbiol. 63, 125-136. doi: 10.1016/S0378-1135(98) 00231-4
179. Zheng, Q., Chen, D., Li, P., Bi, Z., Cao, R., Zhou, B., et al. (2007). Co-expressing GP5 and M proteins under different promoters in recombinant modified vaccinia virus ankara (rMVA)-based vaccine vector enhanced the humoral and cellular immune responses of porcine reproductive and respiratory syndrome virus (PRRSV). Virus Genes 35, 585-595. doi: 10.1007/s11262-007-0161-5
180. Zhou, E. M., Clavijo, A., Jiang, Z., Ameri-Mahabadi, M., and Zimmerman, J. J. (2004). Induction of auto-anti-idiotypic antibodies specific for antibodies to matrix and envelope glycoprotein from pigs experimentally infected with porcine reproductive and respiratory syndrome virus. Vet. Immunol. Immunopathol. 101, 49-59. doi: 10.1016/j.vetimm.2004.03.007
181. Zhou, L., Ni, Y. Y., Pineyro, P., Cossaboom, C. M., Subramaniam, S., Sanford, B. J., et al. (2013). Broadening the heterologous cross-neutralizing antibody inducing ability of porcine reproductive and respiratory syndrome virus by breeding the GP4 or M genes. PLoS ONE 8:e66645. doi: 10.1371/journal.pone.0066645
182. Zhou, L., Ni, Y. Y., Pineyro, P., Sanford, B. J., Cossaboom, C. M., Dryman, B. A., et al. (2012). DNA shuffling of the GP3 genes of porcine reproductive and respiratory syndrome virus (PRRSV) produces a chimeric virus with an improved cross-neutralizing ability against a heterologous PRRSV strain. Virology 434, 96-109. doi: 10.1016/j.virol.2012.09.005
183. Zhou, L., Wang, Z., Ding, Y., Ge, X., Guo, X., and Yang, H. (2015). NADC30-like strain of porcine reproductive and respiratory syndrome virus, China. Emerg. Infect. Dis. 21, 2256-2257. doi: 10.3201/eid2112. 150360
184. Zimmerman, J. (2003). "Historical overview of PRRS virus," in 2003 PRRS Compendium Producer Edition, eds J. Zimmerman and K. J. Yoon (Des Moines: National Pork Board), 2-7.
185. Zimmerman, J. J., Yoon, K. J., Wills, R. W., and Swenson, S. L. (1997). General overview of PRRSV: a perspective from the United States. Vet. Microbiol. 55, 187-196. doi: 10.1016/S0378-1135(96)01330-2
186. Zuckermann, F. A.,Garcia, E. A., Luque, I. D., Christopher-Hennings, J., Doster, A., Brito, M., et al. (2007). Assessment of the efficacy of commercial porcine reproductive and respiratory syndrome virus (PRRSV) vaccines based on measurement of serologic response, frequency of gamma-IFN-producing cells and virological parameters of protection upon challenge. Vet. Microbiol. 123, 69-85. doi: 10.1016/j.vetmic.2007.02.009