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Pigeon paramyxovirus type 1 variants with polybasic F protein cleavage site but strikingly different pathogenicity

Sandra Heiden1, Christian Grund, Dirk Höper

  • 1Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald-Insel Riems, Germany.

Virus Genes
|September 18, 2014
PubMed

Insights

Newcastle disease virus (NDV) virulence can be modulated by minor genetic changes. Even with a specific protein structure, just two amino acid alterations in the fusion (F) protein and polymerase significantly increased NDV pathogenicity.

Area of Science:

  • Avian Virology
  • Molecular Biology
  • Pathogen Evolution

Background:

  • Newcastle disease virus (NDV), specifically pigeon paramyxovirus type 1 (PPMV-1), typically exhibits mesogenic pathotype.
  • Pigeon NDV strains are characterized by a polybasic amino acid motif at the fusion (F) protein cleavage site.

Purpose of the Study:

  • To investigate the genetic basis of virulence modulation in NDV.
  • To determine the impact of specific amino acid changes on NDV pathogenicity, particularly in the context of a polybasic F protein cleavage site.

Main Methods:

  • Reverse genetics was used to create a recombinant NDV (rR75/98) with a polybasic F protein cleavage site.
  • Intracerebral pathogenicity index (ICPI) was assessed in chickens inoculated with the recombinant virus and a re-isolated strain.
  • Whole genome sequencing was performed to compare the genetic makeup of the original and re-isolated viruses.

Main Results:

  • The recombinant NDV (rR75/98) initially showed lentogenic characteristics (ICPI 0.28).
  • Re-isolation of the virus from chicken brains resulted in increased virulence (ICPI 0.93).
  • Whole genome comparison revealed only two amino acid differences between the lentogenic and virulent strains: one in the F protein and one in the polymerase protein.

Conclusions:

  • A polybasic F protein cleavage site is not sufficient to guarantee high NDV virulence.
  • Minimal genetic alterations, specifically two amino acid changes in the F and polymerase proteins, can significantly increase NDV virulence.
  • These findings highlight the rapid adaptability of NDV and the critical role of specific mutations in virulence.

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