Both Genome Segments Contribute to the Pathogenicity of Very Virulent Infectious Bursal Disease Virus

Abstract

f 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.

The Association of Receptor of Activated Protein Kinase C 1(RACK1) with Infectious Bursal Disease Virus Viral Protein VP5 and Voltage-dependent Anion Channel 2 (VDAC2) Inhibits Apoptosis and Enhances Viral Replication

“…Segment B encodes VP1 (97 kDa), a RNAdependent RNA polymerase (8), affecting viral replication and virulence (2,9,10). Segment A contains two partially overlapping ORFs.…”

Genetic characterization of South American infectious bursal disease virus reveals the existence of a distinct worldwide-spread genetic lineage

“…By studying both segments, it is possible to analyse their coevolution, to detect the occurrence of natural reassortants and to determine the role of VP1 in pathogenicity (Le Nouën et al, 2006;Escaffre et al, 2013). VP1 phylogeny resolves a lineage corresponding to the vvIBDV strain and a nonvvIBDV clade constituted by the remaining strains and serotype 2 viruses (Hon et al, 2006).…”

Infectious Bursal Disease Virus Subverts Autophagic Vacuoles To Promote Viral Maturation and Release

“…IBDV is the most extensively studied virus in this family in terms of our collective understanding of its molecular (2)(3)(4)(5) and cellular (6-9) biology, structure (10,11), and pathogenesis (12); therefore, because the autophagic pathway and its function during double-stranded RNA (dsRNA) virus infection are poorly understood, IBDV is an important model system for dsRNA virus. Avibirnavirus VP2 binds to the pathogen receptor HSP90AA1 and induces autophagy by inactivating the AKTmTOR pathway during the early stage of virus infection (13).…”