Molecular and Structural Bases for the Antigenicity of VP2 of Infectious Bursal Disease Virus

Abstract

Infectious bursal disease virus (IBDV), a member of the family Birnaviridae, is responsible for a highly contagious and economically important disease causing immunosuppression in chickens. IBDV variants isolated in the United States exhibit antigenic drift affecting neutralizing epitopes in the capsid protein VP2. To understand antigenic determinants of the virus, we have used a reverse-genetics approach to introduce selected amino acid changes-individually or in combination-into the VP2 gene of the classical IBDV strain D78. We thus generated a total of 42 mutants with changes in 8 amino acids selected by sequence comparison and their locations on loops P BC and P HI at the tip of the VP2 spikes, as shown by the crystal structure of the virion. The antibody reactivities of the mutants generated were assessed using a panel of five monoclonal antibodies (MAbs). Our results show that a few amino acids of the projecting domain of VP2 control the reactivity pattern. Indeed, the binding of four out of the five MAbs analyzed here is affected by mutations in these loops. Furthermore, their importance is highlighted by the fact that some of the engineered mutants display identical reactivity patterns but have different growth phenotypes. Finally, this analysis shows that a new field strain isolated from a chicken flock in Belgium (Bel-IBDV) represents an IBDV variant with a hitherto unobserved antigenic profile, involving one change (P222S) in the P BC loop. Overall, our data provide important new insights for devising efficient vaccines that protect against circulating IBDV strains.

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

“…The dIBDVs share relevant amino acids markers (222S, 256V, 294L and 299N/S) with both vvIBDV and nonvvIBDV strains. The 222S residue was already reported in the classic Lukert strain, in few vvIBDVs, and in a Belgian isolate that was considered a European variant with a different antigenic profile produced by the P222S change (Rudd et al, 2002;Jackwood & Sommer-Wagner, 2007;Letzel et al, 2007). The 256V and 294L residues are characteristic of the non-vvIBDVs, while the dIBDVs have a 299N, like most non-vvIBDVs, or 299S, as most vvIBDVs.…”

Phylogeographic distribution of very virulent infectious bursal disease virus isolates in the Iberian Peninsula

“…Despite the regions under purifying selection being wider than the hydrophilic peaks, this is most probably a consequence of a hitchhiking effect commonly observed in regions under strong functional constraint (Barton, 2000). Considering that any change within these hydrophilic regions may potentially cause a change in the antigenic features of an isolate (Letzel et al, 2007;Jackwood & Sommer-Wagner, 2011), a strong purifying selection pattern as observed in this study could indicate a lack of a selection-driven immune escape in the evolutive pathway of the virus. Partial VP2 sequences have been widely used in routine diagnosis and epidemiological studies worldwide (Jackwood & Sommer-Wagner, 2011).…”

Anin vivoexperimental model to determine antigenic variations among infectious bursal disease viruses

“…For this purpose, an antigencapture enzyme-linked immunosorbent assay was developed that provided a system for differentiation between different antigenic subtypes of IBDV based on certain reaction patterns using a panel of neutralizing monoclonal antibodies (mAbs; Van der Marel et al, 1990). In-depth analysis of amino acid exchanges causing differences in the antigenicity of IBDV lead to the conclusion that IBDV antigenicity is more complex than expected (Letzel et al, 2007;Icard et al, 2008;Durairaj et al, 2011). It also became clear that amino acid exchanges outside the projection domain might result in antigenic differences (Durairaj et al, 2011).…”