1887

Abstract

A prototype avian metapneumovirus (AMPV) vaccine (P20) was previously shown to give variable outcomes in experimental trials. Following plaque purification, three of 12 viruses obtained from P20 failed to induce protection against virulent challenge, whilst the remainder retained their protective capacity. The genome sequences of two protective viruses were identical to the P20 consensus, whereas two non-protective viruses differed only in the SH gene transcription termination signal. Northern blotting showed that the alterations in the SH gene-end region of the non-protective viruses led to enhanced levels of dicistronic mRNA produced by transcriptional readthrough. A synthetic minigenome was used to demonstrate that the altered SH gene-end region reduced the level of protein expression from a downstream gene. The genomes of the remaining eight plaque-purified viruses were sequenced in the region where the P20 consensus sequence differed from the virulent progenitor. The seven protective clones were identical, whereas the non-protective virus retained the virulent progenitor sequence at two positions and contained extensive alterations in its attachment (G) protein sequence associated with a reduced or altered expression pattern of G protein on Western blots. The data indicate that the efficacy of a putative protective vaccine strain is affected by mutations altering the balance of G protein expression.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82755-0
2007-06-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/6/1767.html?itemId=/content/journal/jgv/10.1099/vir.0.82755-0&mimeType=html&fmt=ahah

References

  1. Bass B. L., Weintraub H., Cattaneo R., Billeter M. A. 1989; Biased hypermutation of viral RNA genomes could be due to unwinding/modification of double-stranded RNA. Cell 56:331 [CrossRef]
    [Google Scholar]
  2. Biacchesi S., Pham Q. N., Skiadopoulos M. H., Murphy B. R., Collins P. L., Buchholz U. J. 2005; Infection of nonhuman primates with recombinant human metapneumovirus lacking the SH, G, or M2-2 protein categorizes each as a nonessential accessory protein and identifies vaccine candidates. J Virol 79:12608–12613 [CrossRef]
    [Google Scholar]
  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. Catelli E., Cecchinato M., Savage C. E., Jones R. C., Naylor C. J. 2006; Demonstration of loss of attenuation and extended field persistence of a live avian metapneumovirus vaccine. Vaccine 24:6476–6482 [CrossRef]
    [Google Scholar]
  5. Cavanagh D., Barrett T. 1988; Pneumovirus-like characteristics of the mRNA and proteins of turkey rhinotracheitis virus. Virus Res 11:241–256 [CrossRef]
    [Google Scholar]
  6. Collins M. S., Gough R. E. 1988; Characterization of a virus associated with turkey rhinotracheitis. J Gen Virol 69:909–916 [CrossRef]
    [Google Scholar]
  7. Edworthy N. L., Easton A. J. 2005; Mutational analysis of the avian pneumovirus conserved transcriptional gene start sequence identifying critical residues. J Gen Virol 86:3343–3347 [CrossRef]
    [Google Scholar]
  8. Johnson T. R., Teng M. N., Collins P. L., Graham B. S. 2004; Respiratory syncytial virus (RSV) G glycoprotein is not necessary for vaccine-enhanced disease induced by immunization with formalin-inactivated RSV. J Virol 78:6024–6032 [CrossRef]
    [Google Scholar]
  9. Jones R. C. 1996; Avian pneumovirus infection: questions still unanswered. Avian Pathol 25:639–648 [CrossRef]
    [Google Scholar]
  10. Jones R. C., Naylor C. J., al-Afaleq A., Worthington K. J., Jones R. 1992; Effect of cyclophosphamide immunosuppression on the immunity of turkeys to viral rhinotracheitis. Res Vet Sci 53:38–41 [CrossRef]
    [Google Scholar]
  11. Ling R., Pringle C. R. 1988; Turkey rhinotracheitis virus: in vivo and in vitro polypeptide synthesis. J Gen Virol 69:917–923 [CrossRef]
    [Google Scholar]
  12. Ling R., Easton A. J., Pringle C. R. 1992; Sequence analysis of the 22K, SH and G genes of turkey rhinotracheitis virus and their intergenic regions reveals a gene order different from that of other pneumoviruses. J Gen Virol 73:1709–1715 [CrossRef]
    [Google Scholar]
  13. Naylor C. J., Jones R. C. 1994; Demonstration of a virulent subpopulation in a prototype live attenuated turkey rhinotracheitis vaccine. Vaccine 12:1225–1230 [CrossRef]
    [Google Scholar]
  14. Naylor C., Shaw K., Britton P., Cavanagh D. 1997a; Appearance of type B avian pneumovirus in Great Britain. Avian Pathol 26:327–338 [CrossRef]
    [Google Scholar]
  15. Naylor C. J., Worthington K. J., Jones R. C. 1997b; Failure of maternal antibodies to protect young turkey poults against challenge with turkey rhinotracheitis virus. Avian Dis 41:968–971 [CrossRef]
    [Google Scholar]
  16. Naylor C. J., Brown P. A., Edworthy N., Ling R., Jones R. C., Savage C. E., Easton A. J. 2004; Development of a reverse-genetics system for Avian pneumovirus demonstrates that the small hydrophobic (SH) and attachment (G) genes are not essential for virus viability. J Gen Virol 85:3219–3227 [CrossRef]
    [Google Scholar]
  17. Randhawa J. S., Wilson S. D., Tolley K. P., Cavanagh D., Pringle C. R., Easton A. J. 1996; Nucleotide sequence of the gene encoding the viral polymerase of avian pneumovirus. J Gen Virol 77:3047–3051 [CrossRef]
    [Google Scholar]
  18. Randhawa J. S., Marriott A. C., Pringle C. R., Easton A. J. 1997; Rescue of synthetic minireplicons establishes the absence of the NS1 and NS2 genes from avian pneumovirus. J Virol 71:9849–9854
    [Google Scholar]
  19. Tran K. C., Collins P. L., Teng M. N. 2004; Effects of altering the transcription termination signals of respiratory syncytial virus on viral gene expression and growth in vitro and in vivo. J Virol 78:692–699 [CrossRef]
    [Google Scholar]
  20. van den Hoogen B. G., Bestebroer T. M., Osterhaus A. D., Fouchier R. A. 2002; Analysis of the genomic sequence of a human metapneumovirus. Virology 295:119–132 [CrossRef]
    [Google Scholar]
  21. Williams R. A., Savage C. E., Jones R. C. 1991a; Development of a live attenuated vaccine against turkey rhinotracheitis. Avian Pathol 20:45–55 [CrossRef]
    [Google Scholar]
  22. Williams R. A., Savage C. E., Worthington K. J., Jones R. C. 1991b; Further studies on the development of a live attenuated vaccine against turkey rhinotracheitis. Avian Pathol 20:585–596 [CrossRef]
    [Google Scholar]
  23. Yu Q., Davis P. J., Brown T. D., Cavanagh D. 1992a; Sequence and in vitro expression of the M2 gene of turkey rhinotracheitis pneumovirus. J Gen Virol 73:1355–1363 [CrossRef]
    [Google Scholar]
  24. Yu Q., Davis P. J., Li J., Cavanagh D. 1992b; Cloning and sequencing of the matrix protein (M) gene of turkey rhinotracheitis virus reveal a gene order different from that of respiratory syncytial virus. Virology 186:426–434 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82755-0
Loading
/content/journal/jgv/10.1099/vir.0.82755-0
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