1887

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus that emerged in the late 1980s in both Europe and North America as the causative agent of porcine reproductive and respiratory syndrome (PRRS), now the most important disease of swine worldwide. Despite extensive characterization of PRRSV proteins by direct analysis and comparison with other arteriviruses, determinants of virulence, pathogenesis and protective immune recognition remain poorly understood. Thus, we hypothesized that additional ORFs are present in the PRRSV genome that may contribute to its biological properties, and so we screened highly purified virions of strain VR2332, the prototype type 2 PRRSV, for evidence of novel polypeptides. A 51 aa polypeptide was discovered that is encoded by an alternative ORF of the subgenomic mRNA encoding the major envelope glycoprotein, GP5, and which is incorporated into virions. The protein, referred to as ORF5a protein, is expressed in infected cells, and pigs infected with PRRSV express anti-ORF5a protein antibodies. A similar ORF is present as an alternative reading frame in all PRRSV subgenomic RNA5 genes and in all other arteriviruses, suggesting that this ORF5a protein plays a significant role in arterivirology. Its discovery also provides a new potential target for immunological and pharmacological intervention in PRRS.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.030213-0
2011-05-01
2020-10-01
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/5/1107.html?itemId=/content/journal/jgv/10.1099/vir.0.030213-0&mimeType=html&fmt=ahah

References

  1. Baker R. B., Yu W., Fuentes M., Johnson C. R., Peterson L., Rossow K., Daniels C. S., Polson D., Murtaugh M. P. 2007; Prairie dog (Cynomys ludovicianus) is not a host for porcine reproductive and respiratory syndrome virus. J Swine Health Prod 15:22–29
    [Google Scholar]
  2. Bayer T. S., Booth L. N., Knudsen S. M., Ellington A. D. 2005; Arginine-rich motifs present multiple interfaces for specific binding by RNA. RNA 11:1848–1857 [CrossRef][PubMed]
    [Google Scholar]
  3. Bryans J. T., Crowe M. E., Doll E. R., McCollum W. H. 1957; Isolation of a filterable agent causing arteritis of horses and abortion by mares; its differentiation from the equine abortion (influenza) virus. Cornell Vet 47:3–41[PubMed]
    [Google Scholar]
  4. Collins J. E., Benfield D. A., Christianson W. T., Harris L., Hennings J. C., Shaw D. P., Goyal S. M., McCullough S., Morrison R. B. 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[PubMed] [CrossRef]
    [Google Scholar]
  5. de Lima M., Ansari I. H., Das P. B., Ku B. J., Martinez-Lobo F. J., Pattnaik A. K., Osorio F. A. 2009; GP3 is a structural component of the PRRSV type II (US) virion. Virology 390:31–36 [CrossRef][PubMed]
    [Google Scholar]
  6. del Val C., Ernst P., Falkenhahn M., Fladerer C., Glatting K. H., Suhai S., Hotz-Wagenblatt A. 2007; ProtSweep, 2Dsweep and DomainSweep: protein analysis suite at DKFZ. Nucleic Acids Res 35:Web Server issueW444–W450 [CrossRef][PubMed]
    [Google Scholar]
  7. Dokland T. 2010; The structural biology of PRRSV. Virus Res 154:86–97 [CrossRef][PubMed]
    [Google Scholar]
  8. Faaberg K. S. 2008; Arterivirus structural proteins and assembly. In Nidoviruses pp. 433 Edited by Perlman S., Gallagher T., Snijder E. J. Washington, DC: American Society for Microbiology;
    [Google Scholar]
  9. Firth A. E., Zevenhoven-Dobbe J. C., Wills N. M., Go Y. Y., Balasuriya U. B. R., Atkins J. F., Snijder E. J., Posthuma C. C. 2011; Discovery of a small arterivirus gene that overlaps the GP5 coding sequence and is important for virus production. J Gen Virol 92:1097–1106 [CrossRef][PubMed]
    [Google Scholar]
  10. Gnanandarajah J. S., Dvorak C. M., Johnson C. R., Murtaugh M. P. 2008; Presence of free haptoglobin alpha 1S-subunit in acute porcine reproductive and respiratory syndrome virus infection. J Gen Virol 89:2746–2753 [CrossRef][PubMed]
    [Google Scholar]
  11. Han W., Wu J. J., Deng X. Y., Cao Z., Yu X. L., Wang C. B., Zhao T. Z., Chen N. H., Hu H. H. et al. 2009; Molecular mutations associated with the in vitro passage of virulent porcine reproductive and respiratory syndrome virus. Virus Genes 38:276–284 [CrossRef][PubMed]
    [Google Scholar]
  12. Hirokawa T., Boon-Chieng S., Mitaku S. 1998; SOSUI: classification and secondary structure prediction system for membrane proteins. Bioinformatics 14:378–379 [CrossRef][PubMed]
    [Google Scholar]
  13. Jeong H. J., Song Y. J., Lee S. W., Lee J. B., Park S. Y., Song C. S., Ha G. W., Oh J. S., Oh Y. K., Choi I. S. 2010; Comparative measurement of cell-mediated immune responses of swine to the M and N proteins of porcine reproductive and respiratory syndrome virus. Clin Vaccine Immunol 17:503–512 [CrossRef][PubMed]
    [Google Scholar]
  14. Johnson C. R., Yu W., Murtaugh M. P. 2007; Cross-reactive antibody responses to nsp1 and nsp2 of Porcine reproductive and respiratory syndrome virus. J Gen Virol 88:1184–1195 [CrossRef][PubMed]
    [Google Scholar]
  15. Käll L., Krogh A., Sonnhammer E. L. 2007; Advantages of combined transmembrane topology and signal peptide prediction – the Phobius web server. Nucleic Acids Res 35:Web Server issueW429–W432 [CrossRef][PubMed]
    [Google Scholar]
  16. Kapphahn R. J., Ethen C. M., Peters E. A., Higgins L., Ferrington D. A. 2003; Modified alpha A crystallin in the retina: altered expression and truncation with aging. Biochemistry 42:15310–15325 [CrossRef][PubMed]
    [Google Scholar]
  17. Kapur V., Elam M. R., Pawlovich T. M., Murtaugh M. P. 1996; Genetic variation in porcine reproductive and respiratory syndrome virus isolates in the midwestern United States. J Gen Virol 77:1271–1276 [CrossRef][PubMed]
    [Google Scholar]
  18. Keffaber K. K. 1989; Reproductive failure of unknown etiology. Swine Pract Newsl 1:1–9
    [Google Scholar]
  19. Kim H. S., Kwang J., Yoon I. J., Joo H. S., Frey M. L. 1993; Enhanced replication of porcine reproductive and respiratory syndrome (PRRS) virus in a homogeneous subpopulation of MA-104 cell line. Arch Virol 133:477–483 [CrossRef][PubMed]
    [Google Scholar]
  20. Kozak M. 1987; An analysis of 5′-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res 15:8125–8148 [CrossRef][PubMed]
    [Google Scholar]
  21. Meng X. J., Paul P. S., Halbur P. G., Morozov I. 1995; Sequence comparison of open reading frames 2 to 5 of low and high virulence United States isolates of porcine reproductive and respiratory syndrome virus. J Gen Virol 76:3181–3188 [CrossRef][PubMed]
    [Google Scholar]
  22. Michelson S. 2004; Consequences of human cytomegalovirus mimicry. Hum Immunol 65:465–475 [CrossRef][PubMed]
    [Google Scholar]
  23. Molina R. M., Cha S. H., Chittick W., Lawson S., Murtaugh M. P., Nelson E. A., Christopher-Hennings J., Yoon K. J., Evans R., Rowland R. 2008; Immune response against porcine reproductive and respiratory syndrome virus during acute and chronic infection. Vet Immunol Immunopathol 126:283–292 [CrossRef][PubMed]
    [Google Scholar]
  24. Mulupuri P., Zimmerman J. J., Hermann J., Johnson C. R., Cano J. P., Yu W., Dee S. A., Murtaugh M. P. 2008; Antigen-specific B-cell responses to porcine reproductive and respiratory syndrome virus infection. J Virol 82:358–370 [CrossRef][PubMed]
    [Google Scholar]
  25. Murtaugh M. P., Elam M. R., Kakach L. T. 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 [CrossRef][PubMed]
    [Google Scholar]
  26. 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[PubMed]
    [Google Scholar]
  27. Nelsestuen G. L., Zhang Y., Martinez M. B., Key N. S., Jilma B., Verneris M., Sinaiko A., Kasthuri R. S. 2005; Plasma protein profiling: unique and stable features of individuals. Proteomics 5:4012–4024 [CrossRef][PubMed]
    [Google Scholar]
  28. 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][PubMed]
    [Google Scholar]
  29. Paton D. J., Brown I. H., Edwards S., Wensvoort G. 1991; ‘Blue ear’ disease of pigs. Vet Rec 128:617 [CrossRef][PubMed]
    [Google Scholar]
  30. Rost B., Yachdav G., Liu J. 2004; The PredictProtein server. Nucleic Acids Res 32:Web Server issueW321–W326 [CrossRef][PubMed]
    [Google Scholar]
  31. Rowson K. E., Adams D. H., Salaman M. H. 1963; Riley’s enzymes elevating virus; a study of the infection in mice and its relation to virus-induced leukaemia. Acta Unio Int Contra Cancrum 19:404–406[PubMed]
    [Google Scholar]
  32. Rozen S., Skaletsky H. 2000; Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386[PubMed]
    [Google Scholar]
  33. Shi M., Lam T. T., Hon C. C., Hui R. K., Faaberg K. S., Wennblom T., Murtaugh M. P., Stadejek T., Leung F. C. 2010; Molecular epidemiology of PRRSV: a phylogenetic perspective. Virus Res 154:7–17 [CrossRef][PubMed]
    [Google Scholar]
  34. Snijder E. J., Meulenberg J. J. 1998; The molecular biology of arteriviruses. J Gen Virol 79:961–979[PubMed]
    [Google Scholar]
  35. Tan R., Frankel A. D. 1998; A novel glutamine-RNA interaction identified by screening libraries in mammalian cells. Proc Natl Acad Sci U S A 95:4247–4252 [CrossRef][PubMed]
    [Google Scholar]
  36. Tauraso N. M., Shelokov A., Palmer A. E., Allen A. M. 1968; Simian hemorrhagic fever. 3. Isolation and characterization of a viral agent. Am J Trop Med Hyg 17:422–431[PubMed]
    [Google Scholar]
  37. Wensvoort G., Terpstra C., Pol J. M., ter Laak E. A., Bloemraad M., de Kluyver E. P., Kragten C., van Buiten L., den Besten A. et al. 1991; Mystery swine disease in The Netherlands: the isolation of Lelystad virus. Vet Q 13:121–130[PubMed] [CrossRef]
    [Google Scholar]
  38. Wootton S. K., Yoo D. 2003; Homo-oligomerization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein and the role of disulfide linkages. J Virol 77:4546–4557 [CrossRef][PubMed]
    [Google Scholar]
  39. Wu W. H., Fang Y., Farwell R., Steffen-Bien M., Rowland R. R., Christopher-Hennings J., Nelson E. A. 2001; A 10-kDa structural protein of porcine reproductive and respiratory syndrome virus encoded by ORF2b. Virology 287:183–191 [CrossRef][PubMed]
    [Google Scholar]
  40. Xie H., Bandhakavi S., Roe M. R., Griffin T. J. 2007; Preparative peptide isoelectric focusing as a tool for improving the identification of lysine-acetylated peptides from complex mixtures. J Proteome Res 6:2019–2026 [CrossRef][PubMed]
    [Google Scholar]
  41. Yuan S., Murtaugh M. P., Faaberg K. S. 2000; Heteroclite subgenomic RNAs are produced in porcine reproductive and respiratory syndrome virus infection. Virology 275:158–169 [CrossRef][PubMed]
    [Google Scholar]
  42. Yuan S., Mickelson D., Murtaugh M. P., Faaberg K. S. 2001; Complete genome comparison of porcine reproductive and respiratory syndrome virus parental and attenuated strains. Virus Res 79:189–200 [CrossRef][PubMed]
    [Google Scholar]
  43. 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][PubMed]
    [Google Scholar]
  44. Zhou L., Yang H. 2010; Porcine reproductive and respiratory syndrome in China. Virus Res 154:31–37 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.030213-0
Loading
/content/journal/jgv/10.1099/vir.0.030213-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error