title: Pigeon paramyxovirus type 1 variants with polybasic F protein cleavage site but strikingly different pathogenicity.
abstract: Newcastle disease viruses (NDV) isolated from pigeons (pigeon paramyxovirus type 1; PPMV-1) are mostly of mesogenic pathotype and characterized by a polybasic amino acid sequence motif at the fusion protein (F) cleavage site. This feature also applies to isolate R75/98 from Germany. Its genome consists of 15,192 nucleotides and it specifies an intracerebral pathogenicity index (ICPI) of 1.1, as is typical for mesogenic NDV. Recombinant R75/98 (rR75/98) derived by reverse genetics also possesses a polybasic F protein cleavage site but exhibits ICPI of 0.28, indicating a lentogenic virus. While ten virus passages of rR75/98 on embryonated chicken eggs did not result in any alteration of virus characteristics, virus which had been re-isolated from the brain of an intracerebrally inoculated chicken showed an increase in virulence, characterized by an ICPI of 0.93. Comparison of whole genome sequences of rR75/98 and re-isolated rR75/98 (RrR75/98) demonstrated only two amino acid differences, one in the F protein (N472 K) and one in the polymerase protein (K2168R). This result indicates that only very few amino acid alterations are sufficient to modulate virus virulence in the presence of a polybasic amino acid sequence at the proteolytic F protein cleavage site.
authors.affiliation: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald-Insel Riems, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Heiden
authors.forename: Christian
authors.initials: C
authors.lastname: Grund
authors.forename: Dirk
authors.initials: D
authors.lastname: Höper
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
authors.forename: Angela
authors.initials: A
authors.lastname: Römer-Oberdörfer
mesh_terms: D000818:Animals; D002642:Chick Embryo; D010856:Columbidae; D016679:Genome, Viral; D005858:Germany; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009521:Newcastle Disease / Q000821:virology*; D009522:Newcastle disease virus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D012367:RNA, Viral / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D014760:Viral Fusion Proteins / Q000235:genetics*; D014774:Virulence
chemical_list: D012367:RNA, Viral; D014760:Viral Fusion Proteins