title: Rotavirus antigenicity is affected by the genetic context and glycosylation of VP7.
abstract: Rotavirus variants resistant to neutralization were selected using monoclonal antibodies (N-MAbs) raised to VP7 of rotavirus G types 2, 3, and 6. Their neutralization resistance patterns and deduced VP7 amino acid sequences were obtained. Variants selected by two G2-specific N-MAbs 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-5 x SA11 (all genes from SA11 virus except that encoding VP7, which was from RV-5 virus) fell into two neutralization resistance groups. The first group showed identical mutations to the variants selected from RV-5 virus. The second group showed antigenic C region mutations, either alone or in combination with a mutation at aa 69. Variants selected from G3 parent viruses glycosylated at position 238 had a mutation at aa 96 in the A region, otherwise a C-region mutation at 211 was selected. Mutations at amino acid positions 94 or 96 were selected by monoclonal antibodies specific for each of the three serotypes. G3-specific monoclonal antibodies also selected mutations at position 148 and the new position of 264. This latter mutation resulted in substitution of aspartic acid for glycine and was located in a highly conserved and hydrophobic region of VP7. A G2-specific N-MAb selected variants with a mutation at aa 190 producing a new, utilized glycosylation site which we propose to be in new antigenic site E. The positions of mutations in antigenic variants and their antigenicity were determined by parental background genes and VP7 glycosylation.
authors.affiliation: School of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Lazdins
authors.forename: B S
authors.initials: BS
authors.lastname: Coulson
authors.forename: C
authors.initials: C
authors.lastname: Kirkwood
authors.forename: M
authors.initials: M
authors.lastname: Dyall-Smith
authors.forename: P J
authors.initials: PJ
authors.lastname: Masendycz
authors.forename: S
authors.initials: S
authors.lastname: Sonza
authors.forename: I H
authors.initials: IH
authors.lastname: Holmes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002213:Capsid / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D036022:Capsid Proteins; D002417:Cattle; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D012401:Rotavirus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D036022:Capsid Proteins; D017931:DNA Primers; D004279:DNA, Viral; C050779:VP7 protein, Rotavirus