MOLECULAR-BASIS OF ANTIGENIC VARIATION IN INFECTIOUS BURSAL DISEASE VIRUS

Four antigenically different strains of infectious bursal disease virus (IBDV), characterized by their reactivities with a panel of neutralizing monoclonal antibodies (MAbs), were selected to determine the molecular basis of antigenic variation. The large genome segment A, encoding the structural proteins of the U.S. variants GLS, DS326, E/Del and the vaccine strain D78, was cloned and sequenced. Comparison of the deduced amino acid sequences of the U.S. variants with other IBDV strains showed that most of the amino acid substitutions occur in the central region between residues 212 to 332, especially in the two hydrophilic regions between residues 212 to 223 and residues 314 to 324 of VP2 protein. By comparing the amino acid sequences of these variant viruses and their reactivities with IBDV specific MAbs, the putative amino acids involved in the formation of virus-neutralizing epitopes were identified. Comparison of the D78 versus PBG98 sequence showed that Gln at position 249 (Gln249) appears to be critical in binding with MAb B69. Similarly, comparison of the U.S. variant sequences with other serotype 1 sequences showed unique substitution(s) at residue Glu321 in GLS, residues Ile286, Asp318, Glu323 in E/Del, and residues Glu311 and Gln320 in DS326, which could be potential residue(s) involved in the recognition of MAb57, MAb67, and MAb179 epitopes, respectively. Comparison of the serotype 1 and serotype 2 sequences revealed that serotype 2 OH strain lacks the conserved amino acid sequence motif, S-W-S-A-S-G-S, found in all virulent strains, as well as the second hydrophilic peak region, indicating a possible role of these residues in the serotype specificty or the pathogenicity of the virus. Phylogenetic analysis of the IBDV proteins indicated that the U.S. variants are antigenically different from geographically distant European viruses.