title: Both genome segments contribute to the pathogenicity of very virulent infectious bursal disease virus.
abstract: Infectious bursal disease virus (IBDV) causes an economically significant disease of chickens worldwide. Very virulent IBDV (vvIBDV) strains have emerged and induce as much as 60% mortality. The molecular basis for vvIBDV pathogenicity is not understood, and the relative contributions of the two genome segments, A and B, to this phenomenon are not known. Isolate 94432 has been shown previously to be genetically related to vvIBDVs but exhibits atypical antigenicity and does not cause mortality. Here the full-length genome of 94432 was determined, and a reverse genetics system was established. The molecular clone was rescued and exhibited the same antigenicity and reduced pathogenicity as isolate 94432. Genetically modified viruses derived from 94432, whose vvIBDV consensus nucleotide sequence was restored in segment A and/or B, were produced, and their pathogenicity was assessed in specific-pathogen-free chickens. We found that a valine (position 321) that modifies the most exposed part of the capsid protein VP2 critically modified the antigenicity and partially reduced the pathogenicity of 94432. However, a threonine (position 276) located in the finger domain of the virus polymerase (VP1) contributed even more significantly to attenuation. This threonine is partially exposed in a hydrophobic groove on the VP1 surface, suggesting possible interactions between VP1 and another, as yet unidentified molecule at this amino acid position. The restored vvIBDV-like pathogenicity was associated with increased replication and lesions in the thymus and spleen. These results demonstrate that both genome segments influence vvIBDV pathogenicity and may provide new targets for the attenuation of vvIBDVs.
authors.affiliation: Anses-French Agency for Food, Environmental and Occupational Health and Safety, Avian and Rabbit Virology, Immunology and Parasitology Unit (VIPAC), OIE Reference Laboratory for Infectious Bursal Disease, Ploufragan, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Escaffre
authors.forename: Cyril
authors.initials: C
authors.lastname: Le Nouën
authors.forename: Michel
authors.initials: M
authors.lastname: Amelot
authors.forename: Xavier
authors.initials: X
authors.lastname: Ambroggio
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Ogden
authors.forename: Olivier
authors.initials: O
authors.lastname: Guionie
authors.forename: Didier
authors.initials: D
authors.lastname: Toquin
authors.forename: Hermann
authors.initials: H
authors.lastname: Müller
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Islam
authors.forename: Nicolas
authors.initials: N
authors.lastname: Eterradossi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018175:Birnaviridae Infections / Q000401:mortality / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D002642:Chick Embryo; D002645:Chickens / Q000821:virology; D007243:Infectious bursal disease virus / Q000235:genetics* / Q000472:pathogenicity*; D056004:Molecular Dynamics Simulation; D011201:Poultry Diseases / Q000473:pathology / Q000821:virology*; D017423:Sequence Analysis, RNA; D013154:Spleen / Q000821:virology; D013950:Thymus Gland / Q000821:virology; D015678:Viral Structural Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: C107669:VP1 protein, infectious bursal disease virus; C082513:VP2 protein, infectious bursal disease virus; D015678:Viral Structural Proteins