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Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen

As with many other viruses, the initial cell attachment of rotaviruses, major causative agent of infantile gastroenteritis, is mediated by interactions with specific cellular glycans(1–4). The distally located VP8* domain of the rotavirus spike protein VP4(5) mediates such interactions. The existing...

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Autores principales: Hu, Liya, Crawford, Sue E., Czako, Rita, Cortes-Penfield, Nicolas W, Smith, David F., Le Pendu, Jacques, Estes, Mary K., Venkataram Prasad, B. V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350622/
https://www.ncbi.nlm.nih.gov/pubmed/22504179
http://dx.doi.org/10.1038/nature10996
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author Hu, Liya
Crawford, Sue E.
Czako, Rita
Cortes-Penfield, Nicolas W
Smith, David F.
Le Pendu, Jacques
Estes, Mary K.
Venkataram Prasad, B. V.
author_facet Hu, Liya
Crawford, Sue E.
Czako, Rita
Cortes-Penfield, Nicolas W
Smith, David F.
Le Pendu, Jacques
Estes, Mary K.
Venkataram Prasad, B. V.
author_sort Hu, Liya
collection PubMed
description As with many other viruses, the initial cell attachment of rotaviruses, major causative agent of infantile gastroenteritis, is mediated by interactions with specific cellular glycans(1–4). The distally located VP8* domain of the rotavirus spike protein VP4(5) mediates such interactions. The existing paradigm is that ‘sialidase-sensitive’ animal rotavirus strains bind to glycans with terminal sialic acid (Sia), whereas ‘sialidase-insensitive’ human rotavirus (HR) strains bind to glycans with internal Sia such as GM1(3). Although the involvement of Sia in the animal strains is firmly supported by crystallographic studies(1,3,6,7), it is not yet known how VP8* of HRs interacts with Sia and whether their cell attachment necessarily involves sialoglycans. We found that VP8* of a HR strain specifically recognizes A-type histo-blood group antigen (HBGA) using a glycan array screen comprised of 511 glycans, and that virus infectivity in HT-29 cells is abrogated by anti-Atype antibodies as well as significantly enhanced in CHO cells genetically modified to express the A-type HBGA, providing a novel paradigm for initial cell attachment of HR. HBGAs are genetically determined glycoconjugates present in mucosal secretions, epithelial and on red blood cells(8), and are recognized as susceptibility and cell attachment factors for gastric pathogens like H. pylori(9) and noroviruses(10). Our crystallographic studies show that the A-type HBGA binds to the HR VP8* at the same location as the Sia in the VP8* of animal rotavirus, and suggest how subtle changes within the same structural framework allow for such receptor switching. These results raise the possibility that host susceptibility to specific HR strains and pathogenesis are influenced by genetically controlled expression of different HBGAs among the world’s population.
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spelling pubmed-33506222012-11-10 Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen Hu, Liya Crawford, Sue E. Czako, Rita Cortes-Penfield, Nicolas W Smith, David F. Le Pendu, Jacques Estes, Mary K. Venkataram Prasad, B. V. Nature Article As with many other viruses, the initial cell attachment of rotaviruses, major causative agent of infantile gastroenteritis, is mediated by interactions with specific cellular glycans(1–4). The distally located VP8* domain of the rotavirus spike protein VP4(5) mediates such interactions. The existing paradigm is that ‘sialidase-sensitive’ animal rotavirus strains bind to glycans with terminal sialic acid (Sia), whereas ‘sialidase-insensitive’ human rotavirus (HR) strains bind to glycans with internal Sia such as GM1(3). Although the involvement of Sia in the animal strains is firmly supported by crystallographic studies(1,3,6,7), it is not yet known how VP8* of HRs interacts with Sia and whether their cell attachment necessarily involves sialoglycans. We found that VP8* of a HR strain specifically recognizes A-type histo-blood group antigen (HBGA) using a glycan array screen comprised of 511 glycans, and that virus infectivity in HT-29 cells is abrogated by anti-Atype antibodies as well as significantly enhanced in CHO cells genetically modified to express the A-type HBGA, providing a novel paradigm for initial cell attachment of HR. HBGAs are genetically determined glycoconjugates present in mucosal secretions, epithelial and on red blood cells(8), and are recognized as susceptibility and cell attachment factors for gastric pathogens like H. pylori(9) and noroviruses(10). Our crystallographic studies show that the A-type HBGA binds to the HR VP8* at the same location as the Sia in the VP8* of animal rotavirus, and suggest how subtle changes within the same structural framework allow for such receptor switching. These results raise the possibility that host susceptibility to specific HR strains and pathogenesis are influenced by genetically controlled expression of different HBGAs among the world’s population. 2012-04-15 /pmc/articles/PMC3350622/ /pubmed/22504179 http://dx.doi.org/10.1038/nature10996 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Hu, Liya
Crawford, Sue E.
Czako, Rita
Cortes-Penfield, Nicolas W
Smith, David F.
Le Pendu, Jacques
Estes, Mary K.
Venkataram Prasad, B. V.
Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen
title Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen
title_full Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen
title_fullStr Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen
title_full_unstemmed Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen
title_short Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen
title_sort cell attachment protein vp8* of a human rotavirus specifically interacts with a-type histo-blood group antigen
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350622/
https://www.ncbi.nlm.nih.gov/pubmed/22504179
http://dx.doi.org/10.1038/nature10996
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