1887

Abstract

Virulence of Newcastle disease virus (NDV) is mainly determined by the amino acid sequence surrounding the fusion (F) protein cleavage site, since host proteases that cleave the F protein of virulent strains are present in more tissues than those that cleave the F protein of non-virulent strains. Nevertheless, comparison of NDV strains that carry exactly the same F protein cleavage site shows that significant differences in virulence still exist. For instance, virulent field strain Herts/33 with the F cleavage site RRQRRF had an intracerebral pathogenicity index of 1·88 compared with 1·28 for strain NDFLtag, which has the same cleavage site. This implies that additional factors contribute to virulence. After generating an infectious clone of Herts/33 (FL-Herts), we were able to map the location of additional virulence factors by exchanging sequences between FL-Herts and NDFLtag. The results showed that, in addition to the F protein cleavage site, the haemagglutinin–neuraminidase (HN) protein also contributed to virulence. The effect of the HN protein on virulence was most prominent after intravenous inoculation. Interestingly, both the stem region and the globular head of the HN protein seem to be involved in determining virulence.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80822-0
2005-06-01
2024-12-05
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/6/vir861759.html?itemId=/content/journal/jgv/10.1099/vir.0.80822-0&mimeType=html&fmt=ahah

References

  1. Alexander D. J. 1997; Newcastle disease and other paramyxovirus infections. In Diseases of Poultry pp  541–569 Edited by Hofstad M. S. Iowa: Iowa State University Press;
    [Google Scholar]
  2. Alexander D. J. 2000; Newcastle disease and other avian paramyxoviruses. Rev Sci Tech 19:443–462
    [Google Scholar]
  3. Alexander D. J. 2001; Newcastle disease. Br Poult Sci 42:5–22 [CrossRef]
    [Google Scholar]
  4. Antin P. B., Ordahl C. P. 1991; Isolation and characterization of an avian myogenic cell line. Dev Biol 143:111–121 [CrossRef]
    [Google Scholar]
  5. Beard C. W., Hanson R. P. 1984; Newcastle disease. In Diseases of Poultry pp  452–470 Edited by Hofstad M. S. Iowa: Iowa State University Press;
    [Google Scholar]
  6. Britton P., Green P., Kottier S., Mawditt K. L., Penzes Z., Cavanagh D., Skinner M. A. 1996; Expression of bacteriophage T7 RNA polymerase in avian and mammalian cells by a recombinant fowlpox virus. J Gen Virol 77:963–970 [CrossRef]
    [Google Scholar]
  7. Brown C., King D. J., Seal B. S. 1999; Pathogenesis of Newcastle disease in chickens experimentally infected with viruses of different virulence. Vet Pathol 36:125–132 [CrossRef]
    [Google Scholar]
  8. Collins M. S., Bashiruddin J. B., Alexander D. J. 1993; Deduced amino acid sequences at the fusion protein cleavage site of Newcastle disease viruses showing variation in antigenicity and pathogenicity. Arch Virol 128:363–370 [CrossRef]
    [Google Scholar]
  9. Crennell S., Takimoto T., Portner A., Taylor G. 2000; Crystal structure of the multifunctional paramyxovirus hemagglutinin–neuraminidase. Nat Struct Biol 7:1068–1074 [CrossRef]
    [Google Scholar]
  10. Curran J., Latorre P., Kolakofsky D. 1998; Translational gymnastics on the Sendai virus P/C mRNA. Semin Virol 8:351–357 [CrossRef]
    [Google Scholar]
  11. de Leeuw O., Peeters B. 1999; Complete nucleotide sequence of Newcastle disease virus: evidence for the existence of a new genus within the subfamily Paramyxovirinae . J Gen Virol 80:131–136
    [Google Scholar]
  12. de Leeuw O. S., Hartog L., Koch G., Peeters B. P. H. 2003; Effect of fusion protein cleavage site mutations on virulence of Newcastle disease virus: non-virulent cleavage site mutants revert to virulence after one passage in chicken brain. J Gen Virol 84:475–484 [CrossRef]
    [Google Scholar]
  13. Deng R., Mirza A. M., Mahon P. J., Iorio R. M. 1997; Functional chimeric HN glycoproteins derived from Newcastle disease virus and human parainfluenza virus-3. Arch Virol 13:S115–S130
    [Google Scholar]
  14. Deng R., Wang Z., Mahon P. J., Marinello M., Mirza A., Iorio R. M. 1999; Mutations in the Newcastle disease virus hemagglutinin–neuraminidase protein that interfere with its ability to interact with the homologous F protein in the promotion of fusion. Virology 253:43–54 [CrossRef]
    [Google Scholar]
  15. Community European. 1992 European Community Council Directive 92/40/EEC, (19 May 1992) Brussels: European Community;
    [Google Scholar]
  16. Community European. 1992 European Community Council Directive 92/66/EEC, (14 July 1992) Brussels: European Community;
    [Google Scholar]
  17. Garten W., Berk W., Nagai Y., Rott R., Klenk H. D. 1980; Mutational changes of the protease susceptibility of glycoprotein F of Newcastle disease virus: effects on pathogenicity. J Gen Virol 50:135–147 [CrossRef]
    [Google Scholar]
  18. Gravel K. A., Morrison T. G. 2003; Interacting domains of the HN and F proteins of Newcastle disease virus. J Virol 77:11040–11049 [CrossRef]
    [Google Scholar]
  19. Huang Z., Krishnamurthy S., Panda A., Samal S. K. 2003; Newcastle disease virus V protein is associated with viral pathogenesis and functions as an alpha interferon antagonist. J Virol 77:8676–8685 [CrossRef]
    [Google Scholar]
  20. Huang Z., Panda A., Elankumaran S., Govindarajan D., Rockemann D. D., Samal S. K. 2004; The hemagglutinin–neuraminidase protein of Newcastle disease virus determines tropism and virulence. J Virol 78:4176–4184 [CrossRef]
    [Google Scholar]
  21. Kawahara N., Yang X. Z., Sakaguchi T., Kiyotani K., Nagai Y., Yoshida T. 1992; Distribution and substrate specificity of intracellular proteolytic processing enzyme(s) for paramyxovirus fusion glycoproteins. J Gen Virol 73:583–590 [CrossRef]
    [Google Scholar]
  22. Krishnamurthy S., Samal S. K. 1998; Nucleotide sequences of the trailer, nucleocapsid protein gene and intergenic regions of Newcastle disease virus strain Beaudette C and completion of the entire genome sequence. J Gen Virol 79:2419–2424
    [Google Scholar]
  23. Lamb R. A., Kolakofsky D. 1996; Paramyxoviridae : the viruses and their replication. In Fundamental Virology pp  1177–1204 Edited by Fields B. N., Knippe D. M., Howley P. M. Philadelphia: Lippincott–Raven;
    [Google Scholar]
  24. Mayo M. A. 2002a; Virus taxonomy – Houston 2002. Arch Virol 147:1071–1076 [CrossRef]
    [Google Scholar]
  25. Mayo M. A. 2002b; A summary of taxonomic changes recently approved by ICTV. Arch Virol 147:1655–1663 [CrossRef]
    [Google Scholar]
  26. Mebatsion T., Verstegen S., de Vaan L. T. C., Römer-Oberdörfer A., Schrier C. C. 2001; A recombinant Newcastle disease virus with low-level V protein expression is immunogenic and lacks pathogenicity for chicken embryos. J Virol 75:420–428 [CrossRef]
    [Google Scholar]
  27. Morrison T. G. 2003; Structure and function of a paramyxovirus fusion protein. Biochim Biophys Acta 1614:73–84 [CrossRef]
    [Google Scholar]
  28. Nagai Y., Klenk H. D., Rott R. 1976; Proteolytic cleavage of the viral glycoproteins and its significance for the virulence of Newcastle disease virus. Virology 72:494–508 [CrossRef]
    [Google Scholar]
  29. Park M.-S., Shaw M. L., Munoz-Jordan J., Cros J. F., Nakaya T., Bouvier N., Palese P., Garcia-Sastre A., Basler C. F. 2003; Newcastle disease virus (NDV)-based assay demonstrates interferon-antagonist activity for the NDV V protein and Nipah virus V, W, and C proteins. J Virol 77:1501–1511 [CrossRef]
    [Google Scholar]
  30. Peeters B. P. H., de Leeuw O. S., Koch G., Gielkens A. L. 1999; Rescue of Newcastle disease virus from cloned cDNA: evidence that cleavability of the fusion protein is a major determinant for virulence. J Virol 73:5001–5009
    [Google Scholar]
  31. Peeters B. P. H., Gruijthuijsen Y. K., de Leeuw O. S., Gielkens A. L. J. 2000; Genome replication of Newcastle disease virus: involvement of the rule-of-six. Arch Virol 145:1829–1845 [CrossRef]
    [Google Scholar]
  32. Peeters B. P. H., de Leeuw O. S., Verstegen I., Koch G., Gielkens A. L. 2001; Generation of a recombinant chimeric Newcastle disease virus vaccine that allows serological differentiation between vaccinated and infected animals. Vaccine 19:1616–1627 [CrossRef]
    [Google Scholar]
  33. Phillips R. J., Samson A. C., Emmerson P. T. 1998; Nucleotide sequence of the 5′-terminus of Newcastle disease virus and assembly of the complete genomic sequence: agreement with the “rule of six”. Arch Virol 143:1993–2002 [CrossRef]
    [Google Scholar]
  34. Rassa J. C., Parks G. D. 1999; Highly diverse intergenic regions of the paramyxovirus simian virus 5 cooperate with the gene end U tract in viral transcription termination and can influence reinitiation at a downstream gene. J Virol 73:3904–3912
    [Google Scholar]
  35. Römer-Oberdörfer A., Mundt E., Mebatsion T., Buchholz U. J., Mettenleiter T. C. 1999; Generation of recombinant lentogenic Newcastle disease virus from cDNA. J Gen Virol 80:2987–2995
    [Google Scholar]
  36. Römer-Oberdörfer A., Werner O., Veits J., Mebatsion T., Mettenleiter T. C. 2003; Contribution of the length of the HN protein and the sequence of the F protein cleavage site to Newcastle disease virus pathogenicity. J Gen Virol 84:3121–3129 [CrossRef]
    [Google Scholar]
  37. Sakaguchi T., Matsuda Y., Kiyokage R., Kawahara N., Kiyotani K., Katunuma N., Nagai Y., Yoshida T. 1991; Identification of endoprotease activity in the trans Golgi membranes of rat liver cells that specifically processes in vitro the fusion glycoprotein precursor of virulent Newcastle disease virus. Virology 184:504–512 [CrossRef]
    [Google Scholar]
  38. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  39. von Messling V., Zimmer G., Herrler G., Haas L., Cattaneo R. 2001; The hemagglutinin of canine distemper virus determines tropism and cytopathogenicity. J Virol 75:6418–6427 [CrossRef]
    [Google Scholar]
  40. Wensvoort G., Terpstra C., Boonstra J., Bloemraad M., van Zaane D. 1986; Production of monoclonal antibodies against swine fever virus and their use in laboratory diagnosis. Vet Microbiol 12:101–108 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.80822-0
Loading
/content/journal/jgv/10.1099/vir.0.80822-0
Loading

Data & Media loading...

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