Histo-Blood Group Antigens Act as Attachment Factors of Rabbit Hemorrhagic Disease Virus Infection in a Virus Strain-Dependent Manner
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Rabbit Hemorrhagic disease virus (RHDV), a calicivirus of the Lagovirus genus, and responsible for rabbit hemorrhagic disease (RHD), kills rabbits between 48 to 72 hours post infection with mortality rates as high as 50-90%. Caliciviruses, including noroviruses and RHDV, have been shown to bind histo-blood group antigens (HBGA) and human non-secretor individuals lacking ABH antigens in epithelia have been found to be resistant to norovirus infection. RHDV virus-like particles have previously been shown to bind the H type 2 and A antigens. In this study we present a comprehensive assessment of the strain-specific binding patterns of different RHDV isolates to HBGAs. We characterized the HBGA expression in the duodenum of wild and domestic rabbits by mass spectrometry and relative quantification of A, B and H type 2 expression. A detailed binding analysis of a range of RHDV strains, to synthetic sugars and human red blood cells, as well as to rabbit duodenum, a likely gastrointestinal site for viral entrance was performed. Enzymatic cleavage of HBGA epitopes confirmed binding specificity. Binding was observed to blood group B, A and H type 2 epitopes in a strain-dependent manner with slight differences in specificity for A, B or H epitopes allowing RHDV strains to preferentially recognize different subgroups of animals. Strains related to the earliest described RHDV outbreak were not able to bind A, whereas all other genotypes have acquired A binding. In an experimental infection study, rabbits lacking the correct HBGA ligands were resistant to lethal RHDV infection at low challenge doses. Similarly, survivors of outbreaks in wild populations showed increased frequency of weak binding phenotypes, indicating selection for host resistance depending on the strain circulating in the population. HBGAs thus act as attachment factors facilitating infection, while their polymorphism of expression could contribute to generate genetic resistance to RHDV at the population level.
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RHDV and human noroviruses bind histo-blood group antigens - complex carbohydrates linked to glycoproteins or glycolipids on the surface of erythrocytes and mucosal epithelial cells.
“while RHDV and human noroviruses bind histo-blood group antigens – complex carbohydrates linked to glycoproteins or glycolipids on the surface of erythrocytes and mucosal epithelial cells [40–42].”
From Vesivirus 2117 capsids more closely resemble sapovirus and lagovirus particles than other known vesivirus structures (2017) · cites this paper as [41]
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- Authors
- Nyström, K., Le Gall-Reculé, G., Grassi, P., Abrantes, J., Ruvoën-Clouet, N., Le Moullac-Vaidye, B., Lopes, A. M., Esteves, P. J., Strive, T., Marchandeau, S., Dell, A., Haslam, S. M., & Le Pendu, J.
- Affiliations
- Inserm (FR)
- Imperial College London (GB)
- Centro de Investigação em Biodiversidade e Recursos Genéticos (PT)
- Cooperativa de Ensino Superior Politécnico e Universitário (PT)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Office National de la Chasse et de la Faune Sauvage (FR)
- Corresponding author
- Nyström, Kristina
- Grassi, Paola
- Abrantes, Joana
- Lopes, Ana M.
- Esteves, Pedro J.
- Strive, Tanja
- Marchandeau, Stéphane
- Dell, Anne
- Haslam, Stuart M.
- ORCID
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-08-25
- Volume
- 7
- Issue
- 8
- Pages
- e1002188
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC3161982
- OpenAlex
- W1988135890
- Cited by
- 114
- References
- 83
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2022: 10 · 2021: 7 · 2020: 10 · 2019: 6 · 2018: 8 · 2017: 9 · 2016: 4 · 2015: 13 · 2014: 14 · 2013: 15 · 2012: 9
- FWCI
- 21.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council (BB/F008309/1)
- Fundação para a Ciência e a Tecnologia (SFRH/BD/31048/2006, PTDC/CVT/108490/2008)
- FP7 People: Marie-Curie Actions
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Infectious Diseases › Viral gastroenteritis research and epidemiology
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- rabbit hemorrhagic disease virus, histo-blood group antigens, viral attachment, ABH blood group antigens, duodenum, host resistance, calicivirus, norovirus, wild rabbits, host-virus coevolution, antigenic polymorphism
- MeSH terms
- Animals, Epitopes, Australia, Blood Group Antigens, DNA, Viral, Duodenum, Hemagglutination, Viral, Immunohistochemistry, Phenotype, Phylogeny, Protein Binding, Rabbits, Mass Spectrometry, Caliciviridae Infections, Hemorrhagic Disease Virus, Rabbit
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