Affinities of recombinant norovirus P dimers for human blood group antigens.

ABSTRACT: Noroviruses (NoVs), the major cause of viral acute gastroenteritis, recognize histo-blood group antigens (HBGAs) as receptors or attachment factors. To gain a deeper understanding of the interplay between NoVs and their hosts, the affinities of recombinant P dimers (P?'s) of a GII.4 NoV (VA387) to a library of 41 soluble analogs of HBGAs were measured using the direct electrospray ionization mass spectrometry assay. The HBGAs contained the A, B, H and Lewis epitopes, with variable sizes (2-6 residues) and different types (1-6). The results reveal that the P?'s exhibit a broad specificity for the HBGAs and bind to all of the oligosaccharides tested. Overall, the affinities are relatively low, ranging from 400 to 3000 M?¹ and are influenced by the chain type: 3 > 1 ? 2 ? 4 ? 5 ? 6 for H antigens; 6 > 1 ? 3 ? 4 ? 5 > 2 for A antigens; 3 > 1 ? 4 ? 5 ? 6 > 2 for B antigens, but not by chain length. The highest-affinity ligands are B type 3 (3000 ± 300 M?¹) and A type 6 (2350 ± 60 M?¹). While the higher affinity to the type 3 H antigen was previously observed, preferential binding to the types 6 and 3 antigens with A and B epitopes, respectively, has not been previously reported. A truncated P domain dimer (lacking the C-terminal arginine cluster) exhibits similar binding. The central-binding motifs in the HBGAs were identified by molecular-docking simulations.

SUBMITTER: Han L 

PROVIDER: S-EPMC3555502 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature