title: Different domains of the RNA polymerase of infectious bursal disease virus contribute to virulence.
abstract: BACKGROUND
  Infectious bursal disease virus (IBDV) is a pathogen of worldwide significance to the poultry industry. IBDV has a bi-segmented double-stranded RNA genome. Segments A and B encode the capsid, ribonucleoprotein and non-structural proteins, or the virus polymerase (RdRp), respectively. Since the late eighties, very virulent (vv) IBDV strains have emerged in Europe inducing up to 60% mortality. Although some progress has been made in understanding the molecular biology of IBDV, the molecular basis for the pathogenicity of vvIBDV is still not fully understood.
  
  
  RESULTS
  Strain 88180 belongs to a lineage of pathogenic IBDV phylogenetically related to vvIBDV. By reverse genetics, we rescued a molecular clone (mc88180), as pathogenic as its parent strain. To study the molecular basis for 88180 pathogenicity, we constructed and characterized in vivo reassortant or mosaic recombinant viruses derived from the 88180 and the attenuated Cu-1 IBDV strains. The reassortant virus rescued from segments A of 88180 (A88) and B of Cu-1 (BCU1) was milder than mc88180 showing that segment B is involved in 88180 pathogenicity. Next, the exchange of different regions of BCU1 with their counterparts in B88 in association with A88 did not fully restore a virulence equivalent to mc88180. This demonstrated that several regions if not the whole B88 are essential for the in vivo pathogenicity of 88180.
  The present results show that different domains of the RdRp, are essential for the in vivo pathogenicity of IBDV, independently of the replication efficiency of the mosaic viruses.
authors.affiliation: Avian and Rabbit Virology, Immunology and Parasitology Unit, OIE Reference Laboratory for Infectious Bursal Disease, French Agency for Food, Environmental and Occupational Health Safety (Anses), Ploufragan, France.
authors.forename: Cyril Le
authors.initials: CL
authors.lastname: Nouën
authors.forename: Didier
authors.initials: D
authors.lastname: Toquin
authors.forename: Hermann
authors.initials: H
authors.lastname: Müller
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Raue
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Kean
authors.forename: Patrick
authors.initials: P
authors.lastname: Langlois
authors.forename: Martine
authors.initials: M
authors.lastname: Cherbonnel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Eterradossi
mesh_terms: D000596:Amino Acids / Q000235:genetics; D000818:Animals; D018175:Birnaviridae Infections / Q000201:enzymology* / Q000821:virology*; D002460:Cell Line; D002645:Chickens / Q000821:virology; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016679:Genome, Viral / Q000235:genetics; D007243:Infectious bursal disease virus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D009030:Mosaicism; D009711:Nucleotides / Q000235:genetics; D010641:Phenotype; D011201:Poultry Diseases / Q000201:enzymology / Q000821:virology; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D000596:Amino Acids; D009711:Nucleotides; D012321:DNA-Directed RNA Polymerases