Coding sequences of both genome segments of a European 'very virulent' infectious bursal disease virus

The sequences of segment A (encoding the VP2-VP4-VP3 polyprotein and VP5) and segment B (encoding VP1) of a recent, 'very virulent' (VV) European isolate (UK661) of infectious bursal disease virus (IBDV), a birnavirus, have been determined. There are 26 to 36 amino acid substitutions compared to any other type I IBDV within the segment A polyprotein (of these, 15 are unique) and about 50 substitutions within VP1 (of which 16 are unique). There is more variation compared to classical and antigenic variant viruses, of both virulent and attenuated phenotype, in VP1, VP3 and VP4 than in VP2, even though the latter has previously been identified as the most variable protein between different strains of type I IBDV. In VP3 and VP4, UK661 is the most diverged type I IBDV. Thus the origin of the virus is unclear. It is possible that strong functional constraints have preferentially maintained the primary structure of VP2, though the possibility of recombination cannot be excluded. There are no clear candidate mutations to account for the enhanced virulence of the VV IBDV. Polymerase motifs are well conserved in VP1 but there is an amino acid substitution next to the predicted active-site serine of the viral protease (VP4). In addition, there is a conservative substitution close to the postulated VP2-VP4 cleavage site. It is also now apparent that sequences of IBDV segment B (the segment encoding the RNA polymerase) do not group according to serotype (specified by the capsid proteins encoded on segment A), indicating that segment reassortment has occurred.