1887

Abstract

Newcastle disease virus (NDV) possesses two envelope spike glycoproteins: the haemagglutinin–neuraminidase (HN) protein and the fusion (F) protein. The HN protein, which is responsible for virus attachment to sialic acid-containing receptors, varies in length due to differences in the sizes of the ORFs. An HN protein precursor of 616 aa has been found in avirulent but not in virulent NDV strains, whereas an HN protein of 571 aa can be detected in highly virulent strains only. An HN protein of 577 aa is present in virulent and avirulent strains. The F protein, which mediates virus–cell fusion, requires proteolytic activation at an internal cleavage site, whose amino acid composition determines cleavability by various proteases. Here, the functional significance of the length of the HN protein in combination with F protein cleavage sites typical for virulent (velogenic and mesogenic) or avirulent (lentogenic) strains was investigated. To this end, site-directed mutagenesis was used to construct recombinant NDV on the basis of an infectious clone of the lentogenic vaccine virus Clone-30. Only recombinant NDV expressing an F protein with a multibasic cleavage site typical of virulent strains was able to spread efficiently in cell culture, irrespective of the size of the HN protein. Moreover, as determined by the intracerebral pathogenicity index (ICPI) in 1-day-old, specific-pathogen-free chickens, pathogenicity was influenced by the cleavability of the F protein and not by the length of the HN protein. The maximum ICPI value obtained for these recombinants was 1·3, as compared to a possible maximum of 2. This demonstrates that the modifications introduced did not result in the conversion of the lentogenic Clone-30 to a velogenic strain with an ICPI value of >1·5 and suggests the involvement of additional virulence determinants that contribute to the pathogenicity of NDV.

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2003-11-01
2019-10-20
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References

  1. Alexander, D. J. ( 1997; ). Newcastle disease and other avian Paramyxoviridae infections. In Diseases of Poultry, 10th edn, pp. 541–569. Edited by B. W. Calnek. Ames, IA: Iowa State University Press.
  2. Alexander, D. J. ( 1998; ). Newcastle disease and other avian paramyxoviruses. In A Laboratory Manual for the Isolation and Identification of Avian Pathogens, pp. 156–163. Edited by H. G. Purchase & L. H. Arp. Kennett Square: American Association of Avian Pathologists.
  3. Buchholz, U. J., Finke, S. & Conzelmann, K. K. ( 1999; ). Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. J Virol 73, 251–259.
    [Google Scholar]
  4. CEC ( 1992; ). Council Directive 92/66/EEC, introducing community measures for the control of Newcastle disease, L 260, pp. 1–20. Official Journal of the European Community.
  5. 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]
  6. de Leeuw, O. S., Hartog, L., Koch, G. & Peeters, B. P. ( 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]
  7. 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]
  8. Glickman, R. L., Syddall, R. J., Iorio, R. M., Sheehan, J. P. & Bratt, M. A. ( 1988; ). Quantitative basic residue requirements in the cleavage-activation site of the fusion glycoprotein as a determinant of virulence for Newcastle disease virus. J Virol 62, 354–356.
    [Google Scholar]
  9. Gorman, J. J., Nestorowicz, A., Mitchell, S. J., Corino, G. L. & Selleck, P. W. ( 1988; ). Characterization of the sites of proteolytic activation of Newcastle disease virus membrane glycoprotein precursors. J Biol Chem 263, 12522–12531.
    [Google Scholar]
  10. Gorman, J. J., Hodder, A. N., Selleck, P. W. & Hansson, E. ( 1992; ). Antipeptide antibodies for analysis of pathotype-specific variations in cleavage activation of the membrane glycoprotein precursors of Newcastle disease virus isolates in cultured cells. J Virol Methods 37, 55–70.[CrossRef]
    [Google Scholar]
  11. Gotoh, B., Ogasawara, T., Toyoda, T., Inocencio, N. M., Hamaguchi, M. & Nagai, Y. ( 1990; ). An endoprotease homologous to the blood clotting factor X as a determinant of viral tropism in chick embryo. EMBO J 9, 4189–4195.
    [Google Scholar]
  12. Gotoh, B., Ohnishi, Y., Inocencio, N. M., Esaki, E., Nakayama, K., Barr, P. J., Thomas, G. & Nagai, Y. ( 1992; ). Mammalian subtilisin-related proteinases in cleavage activation of the paramyxovirus fusion glycoprotein: superiority of furin/PACE to PC2 or PC1/PC3. J Virol 66, 6391–6397.
    [Google Scholar]
  13. Kido, H., Yokogoshi, Y., Sakai, K., Tashiro, M., Kishino, Y., Fukutomi, A. & Katunuma, N. ( 1992; ). Isolation and characterization of novel trypsin-like protease found in rat bronchiolar epithelial Clara cells. A possible activator of the viral fusion glycoprotein. J Biol Chem 267, 13573–13579.
    [Google Scholar]
  14. Kolakofsky, D., Pelet, T., Garcin, D., Hausmann, S., Curran, J. & Roux, L. ( 1998; ). Paramyxovirus RNA synthesis and the requirement for hexamer genome length: the rule of six revisited. J Virol 72, 891–899.
    [Google Scholar]
  15. 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]
  16. Krishnamurthy, S., Huang, Z. & Samal, S. K. ( 2000; ). Recovery of a virulent strain of Newcastle disease virus from cloned cDNA: expression of a foreign gene results in growth retardation and attenuation. Virology 278, 168–182.[CrossRef]
    [Google Scholar]
  17. Lamb, R. A. & Kolakofsky, D. ( 2001; ). Paramyxoviridae: the viruses and their replication. In Fields Virology, pp. 1305–1340. Edited by D. M. Knipe & P. M. Howley. Philadelphia: Lippincott Williams & Wilkins.
  18. Mayo, M. A. ( 2002a; ). Virus taxonomy – Houston 2002. Arch Virol 147, 1071–1076.[CrossRef]
    [Google Scholar]
  19. Mayo, M. A. ( 2002b; ). A summary of taxonomic changes recently approved by ICTV. Arch Virol 147, 1655–1663.[CrossRef]
    [Google Scholar]
  20. Mebatsion, T., Verstegen, S., De Vaan, L. T., 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]
  21. Morrison, T. & Portner, A. ( 1991; ). Structure, function, and intracellular processing of the glycoproteins of Paramyxoviridae. In Paramyxoviruses, pp. 347–382. Edited by D. W. Kingsbury. New York: Plenum.
  22. Nagai, Y. ( 1993; ). Protease-dependent virus tropism and pathogenicity. Trends Microbiol 1, 81–87; erratum 1, 1.
    [Google Scholar]
  23. Nagai, Y. & Klenk, H. D. ( 1977; ). Activation of precursors to both glycoproteins of Newcastle disease virus by proteolytic cleavage. Virology 77, 125–134.[CrossRef]
    [Google Scholar]
  24. 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]
  25. Nagai, Y., Shimokata, K., Yoshida, T., Hamaguchi, M., Iinuma, M., Maeno, K., Matsumoto, T., Klenk, H. D. & Rott, R. ( 1979; ). The spread of a pathogenic and an apathogenic strain of Newcastle disease virus in the chick embryo as depending on the protease sensitivity of the virus glycoproteins. J Gen Virol 45, 263–272.[CrossRef]
    [Google Scholar]
  26. Nagai, Y., Hamaguchi, M. & Toyoda, T. ( 1989; ). Molecular biology of Newcastle disease virus. Prog Vet Microbiol Immunol 5, 16–64.
    [Google Scholar]
  27. Peeters, B. P., 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]
  28. Peeters, B. P., Gruijthuijsen, Y. K., de Leeuw, O. S. & Gielkens, A. L. ( 2000; ). Genome replication of Newcastle disease virus: involvement of the rule-of-six. Arch Virol 145, 1829–1845.[CrossRef]
    [Google Scholar]
  29. 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]
  30. Sakaguchi, T., Toyoda, T., Gotoh, B., Inocencio, N. M., Kuma, K., Miyata, T. & Nagai, Y. ( 1989; ). Newcastle disease virus evolution. I. Multiple lineages defined by sequence variability of the hemagglutinin–neuraminidase gene. Virology 169, 260–272.[CrossRef]
    [Google Scholar]
  31. Sato, H., Hattori, S., Ishida, N., Imamura, Y. & Kawakita, M. ( 1987; ). Nucleotide sequence of the hemagglutinin–neuraminidase gene of Newcastle disease virus avirulent strain D26: evidence for a longer coding region with a carboxyl terminal extension as compared to virulent strains. Virus Res 8, 217–232.[CrossRef]
    [Google Scholar]
  32. Scheid, A. & Choppin, P. W. ( 1973; ). Isolation and purification of the envelope proteins of Newcastle disease virus. J Virol 11, 263–271.
    [Google Scholar]
  33. Schuy, W., Garten, W., Linder, D. & Klenk, H. D. ( 1984; ). The carboxyterminus of the hemagglutinin–neuraminidase of Newcastle disease virus is exposed at the surface of the viral envelope. Virus Res 1, 415–426.[CrossRef]
    [Google Scholar]
  34. Steward, M., Vipond, I. B., Millar, N. S. & Emmerson, P. T. ( 1993; ). RNA editing in Newcastle disease virus. J Gen Virol 74, 2539–2547.[CrossRef]
    [Google Scholar]
  35. Toyoda, T., Sakaguchi, T., Imai, K., Inocencio, N. M., Gotoh, B., Hamaguchi, M. & Nagai, Y. ( 1987; ). Structural comparison of the cleavage-activation site of the fusion glycoprotein between virulent and avirulent strains of Newcastle disease virus. Virology 158, 242–247.[CrossRef]
    [Google Scholar]
  36. Toyoda, T., Sakaguchi, T., Hirota, H., Gotoh, B., Kuma, K., Miyata, T. & Nagai, Y. ( 1989; ). Newcastle disease evolution. II. Lack of gene recombination in generating virulent and avirulent strains. Virology 169, 273–282.[CrossRef]
    [Google Scholar]
  37. Werner, O., Römer-Oberdörfer, A., Köllner, B., Manvell, R. J. & Alexander, D. J. ( 1999; ). Characterization of avian paramyxovirus type 1 strains isolated in Germany during 1992 to 1996. Avian Pathol 28, 79–88.[CrossRef]
    [Google Scholar]
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