Molecular and structural bases for the antigenicity of VP2 of infectious bursal disease virus.
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.
Letzel
Tobias
T
Institute of Molecular Biology, Federal Research Institute for Animal Health, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany.
Coulibaly
Fasseli
F
Rey
Felix A
FA
Delmas
Bernard
B
Jagt
Erik
E
van Loon
Adriaan A M W
AA
Mundt
Egbert
E
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000915:Antibody Affinity; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D007243:Infectious bursal disease virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; C082513:VP2 protein, infectious bursal disease virus; D015678:Viral Structural Proteins