Simultaneous alteration of residues 279 and 284 of the VP2 major capsid protein of a very virulent Infectious Bursal Disease Virus (vvIBDV) strain did not lead to attenuation in chickens

Abstract

BackgroundCell culture adaptation of very virulent infectious bursal disease virus (vvIBDV) was shown to be mainly associated with the VP2 capsid protein residues 253, 279, and 284. The single mutation A284T proved critical for cell culture tropism, but did not confer efficient virus replication, which at least required one additional mutation, Q253H or D279N. While the double mutation Q253H/A284T was unambiguously shown to confer both efficient replication in cell culture and attenuation in chickens, conflicting results have been reported regarding the replication efficiency of vvIBDV mutants bearing the D279N/A284T double mutation, and no data are hitherto available on their virulence in chickens.FindingsHere we used an in vivo reverse genetics system to assess the impact of the D279N/A284T double mutation on the replication and attenuation of a chimeric IBDV virus, whose polyprotein derived from a non-culturable vvIBDV clinical isolate. We found that the D279N/A284T double mutation did indeed confer efficient replication in chicken embryo fibroblast (CEF) cell culture, but the mutant virus remained highly pathogenic to chickens.ConclusionsThe double mutation D279N/A284T of the VP2 major capsid protein of vvIBDV is sufficient to confer cell culture tropism and replication efficiency, but does not necessarily lead to virus attenuation.

Further evidence for very virulent infectious bursal disease virus in vaccinated chickens in Nigeria

“…Virulence classification groups these viruses into classical virulent (cv), subclinical variant, and very virulent (vv) IBDV strains (Ben Abdeljelil et al 2014).…”

Molecular characteristics and evolutionary analysis of a very virulent infectious bursal disease virus

“…Virulence declined rapidly when vvIBDV with amino acid mutations at positions 253 and 284 in the VP2 hypervariable region was passaged serially in chicken embryo fibroblast cells [18], while the very virulent pathogenicity was restored after a reverse mutation assay. Recent virulence and immunology studies have shown that the amino acid residue at position 253 is critical to the alteration of virulence of IBDV, while the residues at positions 279 and 284 are not directly related to viral virulence but are involved in cell adaptability and replication efficiency [19,20]. All these studies suggest that a few amino acid mutations at key positions in the VP2 hypervariable region can have significant impacts on the virulence of IBDV.…”

Molecular characterization of Infectious Bursal Disease Virus isolated in Chile reveals several mutations in VP2 coding region and a reassortment in its genome

“…Position 279 has been shown to be involved in the ability to replicate in chicken embryonic fibroblasts (Lim et al 1999 ). However, this does not necessarily imply a lack of pathogenicity in chickens (Abdeljelil et al 2014 ). In addition, 279 residue have been described as one of the positions affected by passages in DT40 cells, which are a tumor cell line derived from the bursa of Fabricius of a chicken infected with avian leukosis virus (Terasaki et al 2008 ; Delgui et al 2009 ).…”