1887

Abstract

The Newcastle disease virus (NDV) matrix (M) protein is a highly basic and nucleocytoplasmic shuttling viral protein. Previous study has demonstrated that the N-terminal 100 aa of NDV M protein are somewhat acidic overall, but the remainder of the polypeptide is strongly basic. In this study, we investigated the role of the N-terminal basic residues in the subcellular localization of M protein and in the replication and pathogenicity of NDV. We found that mutation of the basic residue arginine (R) to alanine (A) at position 42 disrupted M’s nuclear localization. Moreover, a recombinant virus with R42A mutation in the M protein reduced viral replication in DF-1 cells and attenuated the virulence and pathogenicity of the virus in chickens. This is the first report to show that a basic residue mutation in the NDV M protein abrogates its nuclear localization and attenuates viral replication and pathogenicity.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.062992-0
2014-05-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/5/1067.html?itemId=/content/journal/jgv/10.1099/vir.0.062992-0&mimeType=html&fmt=ahah

References

  1. Alexander D. J. 1989; Newcastle disease. In A Laboratory Manual for the Isolation and Identification of Avian Pathogens, 3rd edn. pp. 114–120 Edited by Purchase H. G., Arp L. H., Domermuth C. H., Pearson J. E. Kennett Square, PA: American Association for Avian Pathologists, Inc;
    [Google Scholar]
  2. Alexander D. J. 2000; Newcastle disease and other avian paramyxoviruses. Rev Sci Tech 19:443–462[PubMed]
    [Google Scholar]
  3. Bellini W. J., Englund G., Richardson C. D., Rozenblatt S., Lazzarini R. A. 1986; Matrix genes of measles virus and canine distemper virus: cloning, nucleotide sequences, and deduced amino acid sequences. J Virol 58:408–416[PubMed]
    [Google Scholar]
  4. Blumberg B. M., Rose K., Simona M. G., Roux L., Giorgi C., Kolakofsky D. 1984; Analysis of the Sendai virus M gene and protein. J Virol 52:656–663[PubMed]
    [Google Scholar]
  5. Chambers P., Millar N. S., Platt S. G., Emmerson P. T. 1986; Nucleotide sequence of the gene encoding the matrix protein of Newcastle disease virus. Nucleic Acids Res 14:9051–9061 [View Article][PubMed]
    [Google Scholar]
  6. Coleman N. A., Peeples M. E. 1993; The matrix protein of Newcastle disease virus localizes to the nucleus via a bipartite nuclear localization signal. Virology 195:596–607 [View Article][PubMed]
    [Google Scholar]
  7. Cornax I., Diel D. G., Rue C. A., Estevez C., Yu Q., Miller P. J., Afonso C. L. 2013; Newcastle disease virus fusion and haemagglutinin-neuraminidase proteins contribute to its macrophage host range. J Gen Virol 94:1189–1194 [View Article][PubMed]
    [Google Scholar]
  8. Dortmans J. C., Koch G., Rottier P. J., Peeters B. P. 2009; Virulence of pigeon paramyxovirus type 1 does not always correlate with the cleavability of its fusion protein. J Gen Virol 90:2746–2750 [View Article][PubMed]
    [Google Scholar]
  9. Duan Z., Li Q., He L., Zhao G., Chen J., Hu S., Liu X. 2013; Application of green fluorescent protein-labeled assay for the study of subcellular localization of Newcastle disease virus matrix protein. J Virol Methods 194:118–122 [View Article][PubMed]
    [Google Scholar]
  10. Duan Z., Hu Z., Zhu J., Xu H., Chen J., Liu H., Hu S., Liu X. 2014; Mutations in the FPIV motif of Newcastle disease virus matrix protein attenuate virus replication and reduce virus budding. Arch Virol 159: [View Article][PubMed]
    [Google Scholar]
  11. Estevez C., King D. J., Luo M., Yu Q. 2011; A single amino acid substitution in the haemagglutinin-neuraminidase protein of Newcastle disease virus results in increased fusion promotion and decreased neuraminidase activities without changes in virus pathotype. J Gen Virol 92:544–551 [View Article][PubMed]
    [Google Scholar]
  12. Harrison M. S., Sakaguchi T., Schmitt A. P. 2010; Paramyxovirus assembly and budding: building particles that transmit infections. Int J Biochem Cell Biol 42:1416–1429 [View Article][PubMed]
    [Google Scholar]
  13. Hu S.-L., Sun Q., Wang Q.-Z., Liu Y.-L., Wu Y.-T., Liu X.-F. 2007; Rescue and preliminary application of a recombinant Newcastle disease virus expressing green fluorescent protein gene. Virol Sin 22:34–40 [View Article]
    [Google Scholar]
  14. Hu Z., Hu S., Meng C., Wang X., Zhu J., Liu X. 2011; Generation of a genotype VII Newcastle disease virus vaccine candidate with high yield in embryonated chicken eggs. Avian Dis 55:391–397 [View Article][PubMed]
    [Google Scholar]
  15. Huang Y., Wan H. Q., Liu H. Q., Wu Y. T., Liu X. F. 2004; Genomic sequence of an isolate of Newcastle disease virus isolated from an outbreak in geese: a novel six nucleotide insertion in the non-coding region of the nucleoprotein gene. Brief Report. Arch Virol 149:1445–1457 [View Article][PubMed]
    [Google Scholar]
  16. Iwasaki M., Takeda M., Shirogane Y., Nakatsu Y., Nakamura T., Yanagi Y. 2009; The matrix protein of measles virus regulates viral RNA synthesis and assembly by interacting with the nucleocapsid protein. J Virol 83:10374–10383 [View Article][PubMed]
    [Google Scholar]
  17. Klenk H. D., Nagai Y., Rott R., Nicolau C. 1977; The structure and function of paramyxovirus glycoproteins. Med Microbiol Immunol (Berl) 164:35–47 [View Article][PubMed]
    [Google Scholar]
  18. Mayo M. A. 2002; A summary of taxonomic changes recently approved by ICTV. Arch Virol 147:1655–1663 [View Article][PubMed]
    [Google Scholar]
  19. 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 [View Article][PubMed]
    [Google Scholar]
  20. Nair R., Carter P., Rost B. 2003; NLSdb: database of nuclear localization signals. Nucleic Acids Res 31:397–399 [View Article][PubMed]
    [Google Scholar]
  21. Negovetich N. J., Webster R. G. 2010; Thermostability of subpopulations of H2N3 influenza virus isolates from mallard ducks. J Virol 84:9369–9376 [View Article][PubMed]
    [Google Scholar]
  22. Panda A., Huang Z., Elankumaran S., Rockemann D. D., Samal S. K. 2004; Role of fusion protein cleavage site in the virulence of Newcastle disease virus. Microb Pathog 36:1–10 [View Article][PubMed]
    [Google Scholar]
  23. Pantua H. D., McGinnes L. W., Peeples M. E., Morrison T. G. 2006; Requirements for the assembly and release of Newcastle disease virus-like particles. J Virol 80:11062–11073 [View Article][PubMed]
    [Google Scholar]
  24. Peeples M. E., Wang C., Gupta K. C., Coleman N. 1992; Nuclear entry and nucleolar localization of the Newcastle disease virus (NDV) matrix protein occur early in infection and do not require other NDV proteins. J Virol 66:3263–3269[PubMed]
    [Google Scholar]
  25. 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[PubMed]
    [Google Scholar]
  26. Rajani K. R., Pettit Kneller E. L., McKenzie M. O., Horita D. A., Chou J. W., Lyles D. S. 2012; Complexes of vesicular stomatitis virus matrix protein with host Rae1 and Nup98 involved in inhibition of host transcription. PLoS Pathog 8:e1002929 [View Article][PubMed]
    [Google Scholar]
  27. Reed L. J., Muench H. 1938; A simple method of estimating fifty percent endpoints. Am J Hyg 27:493–497
    [Google Scholar]
  28. Samal S., Kumar S., Khattar S. K., Samal S. K. 2011; A single amino acid change, Q114R, in the cleavage-site sequence of Newcastle disease virus fusion protein attenuates viral replication and pathogenicity. J Gen Virol 92:2333–2338 [View Article][PubMed]
    [Google Scholar]
  29. Samal S., Khattar S. K., Paldurai A., Palaniyandi S., Zhu X., Collins P. L., Samal S. K. 2013; Mutations in the cytoplasmic domain of the Newcastle disease virus fusion protein confer hyperfusogenic phenotypes modulating viral replication and pathogenicity. J Virol 87:10083–10093 [View Article][PubMed]
    [Google Scholar]
  30. Scott M. S., Boisvert F. M., McDowall M. D., Lamond A. I., Barton G. J. 2010; Characterization and prediction of protein nucleolar localization sequences. Nucleic Acids Res 38:7388–7399 [View Article][PubMed]
    [Google Scholar]
  31. Susta L., Miller P. J., Afonso C. L., Estevez C., Yu Q., Zhang J., Brown C. C. 2010; Pathogenicity evaluation of different Newcastle disease virus chimeras in 4-week-old chickens. Trop Anim Health Prod 42:1785–1795 [View Article][PubMed]
    [Google Scholar]
  32. Susta L., Cornax I., Diel D. G., Garcia S. C., Miller P. J., Liu X., Hu S., Brown C. C., Afonso C. L. 2013; Expression of interferon gamma by a highly virulent strain of Newcastle disease virus decreases its pathogenicity in chickens. Microb Pathog 61-62:73–83 [View Article][PubMed]
    [Google Scholar]
  33. Wang Y. E., Park A., Lake M., Pentecost M., Torres B., Yun T. E., Wolf M. C., Holbrook M. R., Freiberg A. N., Lee B. 2010; Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix protein is important for viral budding. PLoS Pathog 6:e1001186 [View Article][PubMed]
    [Google Scholar]
  34. Yin R., Ding Z., Liu X., Mu L., Cong Y., Stoeger T. 2010; Inhibition of Newcastle disease virus replication by RNA interference targeting the matrix protein gene in chicken embryo fibroblasts. J Virol Methods 167:107–111 [View Article][PubMed]
    [Google Scholar]
  35. Yusoff K., Tan W. S. 2001; Newcastle disease virus: macromolecules and opportunities. Avian Pathol 30:439–455 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.062992-0
Loading
/content/journal/jgv/10.1099/vir.0.062992-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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