title: Noroviruses distinguish between type 1 and type 2 histo-blood group antigens for binding.
abstract: Norovirus (NoV) is a causative agent of acute gastroenteritis. NoV binds to histo-blood group antigens (HBGAs), namely, ABH antigens and Lewis (Le) antigens, in which type 1 and type 2 carbohydrate core structures constitute antigenically distinct variants. Norwalk virus, the prototype strain of norovirus, binds to the gastroduodenal junction, and this binding is correlated with the presence of H type 1 antigen but not with that of H type 2 antigen (S. Marionneau, N. Ruvoen, B. Le Moullac-Vaidye, M. Clement, A. Cailleau-Thomas, G. Ruiz-Palacois, P. Huang, X. Jiang, and J. Le Pendu, Gastroenterology 122:1967-1977, 2002). It has been unknown whether NoV distinguishes between the type 1 and type 2 chains of A and B antigens. In this study, we synthesized A type 1, A type 2, B type 1, and B type 2 pentasaccharides in vitro and examined the function of the core structures in the binding between NoV virus-like particles (VLPs) and HBGAs. The attachment of five genogroup I (GI) VLPs from 5 genotypes and 11 GII VLPs from 8 genotypes, GI/1, GI/2, GI/3, GI/4, GI/8, GII/1, GII/3, GII/4, GII/5, GII/6, GII/7, GII/12, and GII/14, to ABH and Le HBGAs was analyzed by enzyme-linked immunosorbent assay-based binding assays and Biacore analyses. GI/1, GI/2, GI/3, GI/4, GI/8, and GII/4 VLPs were more efficiently bound to A type 2 than A type 1, and GI/8 and GII/4 VLPs were more efficiently bound to B type 2 than B type 1, indicating that NoV VLPs distinguish between type 1 and type 2 carbohydrates. The dissociation of GII/4 VLPs from B type 1 was slower than that from B type 2 in the Biacore experiments; moreover, the binding to B type 1 was stronger than that to B type 2 in the ELISA experiments. These results indicated that the type 1 carbohydrates bind more tightly to NoV VLPs than the type 2 carbohydrates. This property may afford NoV tissue specificity. GII/4 is known to be a global epidemic genotype and binds to more HBGAs than other genotypes. This characteristic may be linked with the worldwide transmission of GII/4 strains. GI/2, GI/3, GI/4, GI/8, GII/4, and GII/7 VLPs bound to Le(a) expressed by nonsecretors, suggesting that NoV can infect individuals regardless of secretor phenotype. Overall, our results indicated that HBGAs are important factors in determining tissue specificity and the risk of transmission.
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Musashi-Murayama, Tokyo, Japan. harukos@nih.go.jp
authors.forename: Haruko
authors.initials: H
authors.lastname: Shirato
authors.forename: Satoko
authors.initials: S
authors.lastname: Ogawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ito
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kameyama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiaofan
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Miyamura
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Koji
authors.initials: K
authors.lastname: Ishii
authors.forename: Naokazu
authors.initials: N
authors.lastname: Takeda
mesh_terms: D000328:Adult; D001789:Blood Group Antigens / Q000378:metabolism*; D002240:Carbohydrate Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009663:Norwalk virus / Q000502:physiology*; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000378:metabolism; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D022701:Virosomes; D053585:Virus Attachment
chemical_list: D001789:Blood Group Antigens; D009844:Oligosaccharides; D011991:Receptors, Virus; D022701:Virosomes