ROTAVIRUS ANTIGENICITY IS AFFECTED BY THE GENETIC CONTEXT AND GLYCOSYLATION OF VP7

Rotavirus variants resistant to neutralization were selected using mon oclonal antibodies (N-MAbs) raised to VP7 of rotavirus G types 2, 3, a nd 6. Their neutralization resistance patterns and deduced VP7 amino a cid sequences were obtained. Variants selected by two G2-specific N-MA bs from the homologous parent virus RV-5 showed single amino acid (aa) mutations in the antigenic A region. However, variants selected from reassortant virus RV-5XSA11 (all genes from SA11 virus except that enc oding VP7, which was from RV-5 virus) fell into two neutralization res istance groups. The first group showed identical mutations to the vari ants selected from RV-5 virus. The second group showed antigenic C reg ion mutations, either alone or in combination with a mutation at aa 69 . Variants selected from G3 parent viruses glycosylated at position 23 8 had a mutation at aa 96 in the A region, otherwise a C-region mutati on at 211 was selected. Mutations at amino acid positions 94 or 96 wer e selected by monoclonal antibodies specific for each of the three ser otypes. G3-specific monoclonal antibodies also selected mutations at p osition 148 and the new position of 264. This latter mutation resulted in substitution of aspartic acid for glycine and was located in a hig hly conserved and hydrophobic region of VP7. A G2-specific N-MAb selec ted variants with a mutation at aa 190 producing a new, utilized glyco sylation site which we propose to be in new antigenic site E. The posi tions of mutations in antigenic variants and their antigenicity were d etermined by parental background genes and VP7 glycosylation. (C) 1995 Academic Press, Inc.