Structural basis of P[II] rotavirus evolution and host ranges under selection of histo-blood group antigens

2021 ◽  
Vol 118 (36) ◽  
pp. e2107963118
Author(s):  
Shenyuan Xu ◽  
Kristen Rose McGinnis ◽  
Yang Liu ◽  
Pengwei Huang ◽  
Ming Tan ◽  
...  
Keyword(s):  
Blood Group ◽  
Receptor Binding ◽  
Structural Data ◽  
Structural Basis ◽  
Blood Group Antigens ◽  
Binding Domains ◽  
Animal Populations ◽  
Group A Rotaviruses ◽  
Selection Of

Group A rotaviruses cause severe gastroenteritis in infants and young children worldwide, with P[II] genogroup rotaviruses (RVs) responsible for >90% of global cases. RVs have diverse host ranges in different human and animal populations determined by host histo-blood group antigen (HBGA) receptor polymorphism, but details governing diversity, host ranges, and species barriers remain elusive. In this study, crystal structures of complexes of the major P[II] genogroup P[4] and P[8] genotype RV VP8* receptor–binding domains together with Lewis epitope–containing LNDFH I glycans in combination with VP8* receptor-glycan ligand affinity measurements based on NMR titration experiments revealed the structural basis for RV genotype-specific switching between ββ and βα HBGA receptor–binding sites that determine RV host ranges. The data support the hypothesis that P[II] RV evolution progressed from animals to humans under the selection of type 1 HBGAs guided by stepwise host synthesis of type 1 ABH and Lewis HBGAs. The results help explain disease burden, species barriers, epidemiology, and limited efficacy of current RV vaccines in developing countries. The structural data has the potential to impact the design of future vaccine strategies against RV gastroenteritis.

scholarly journals Structural Basis for the Recognition of Blood Group Trisaccharides by Norovirus

2007 ◽  
Vol 81 (11) ◽  
pp. 5949-5957 ◽  
Author(s):  
Sheng Cao ◽  
Zhiyong Lou ◽  
Ming Tan ◽  
Yutao Chen ◽  
Yijin Liu ◽  
...  
Keyword(s):  
Blood Group ◽  
Receptor Binding ◽  
Structural Basis ◽  
Blood Group Antigens ◽  
Binding Modes ◽  
Receptor Binding Site ◽  
Viral Capsids ◽  
Binding Interface ◽  
P Domain ◽  
Complex Crystal

ABSTRACT Noroviruses are one of the major causes of nonbacterial gastroenteritis epidemics in humans. Recent studies on norovirus receptors show that different noroviruses recognize different human histo-blood group antigens (HBGAs), and eight receptor binding patterns of noroviruses have been identified. The P domain of the norovirus capsids is directly involved in this recognition. To determine the precise locations and receptor binding modes of HBGA carbohydrates on the viral capsids, a recombinant P protein of a GII-4 strain norovirus, VA387, was cocrystallized with synthetic type A or B trisaccharides. Based on complex crystal structures observed at a 2.0-Å resolution, we demonstrated that the receptor binding site lies at the outermost end of the P domain and forms an extensive hydrogen-bonding network with the saccharide ligand. The A and B trisaccharides display similar binding modes, and the common fucose ring plays a key role in this interaction. The extensive interface between the two protomers in a P dimer also plays a crucial role in the formation of the receptor binding interface.

scholarly journals Bat Caliciviruses and Human Noroviruses Are Antigenically Similar and Have Overlapping Histo-Blood Group Antigen Binding Profiles

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Jacob F. Kocher ◽  
Lisa C. Lindesmith ◽  
Kari Debbink ◽  
Anne Beall ◽  
Michael L. Mallory ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Homology Modeling ◽  
Blood Group ◽  
Receptor Binding ◽  
Wild Animal ◽  
Blood Group Antigens ◽  
Viral Pathogens ◽  
Human Noroviruses ◽  
Animal Populations ◽  
Antigenic Epitopes

ABSTRACTEmerging zoonotic viral diseases remain a challenge to global public health. Recent surveillance studies have implicated bats as potential reservoirs for a number of viral pathogens, including coronaviruses and Ebola viruses.Caliciviridaerepresent a major viral family contributing to emerging diseases in both human and animal populations and have been recently identified in bats. In this study, we blended metagenomics, phylogenetics, homology modeling, andin vitroassays to characterize two novel bat calicivirus (BtCalV) capsid sequences, corresponding to strain BtCalV/A10/USA/2009, identified inPerimyotis subflavusnear Little Orleans, MD, and bat norovirus. We observed that bat norovirus formed virus-like particles and had epitopes and receptor-binding patterns similar to those of human noroviruses. To determine whether these observations stretch across multiple bat caliciviruses, we characterized a novel bat calicivirus, BtCalV/A10/USA/2009. Phylogenetic analysis revealed that BtCalV/A10/USA/2009 likely represents a novelCaliciviridaegenus and is most closely related to "recoviruses." Homology modeling revealed that the capsid sequences of BtCalV/A10/USA/2009 and bat norovirus resembled human norovirus capsid sequences and retained host ligand binding within the receptor-binding domains similar to that seen with human noroviruses. Both caliciviruses bound histo-blood group antigens in patterns that overlapped those seen with human and animal noroviruses. Taken together, our results indicate the potential for bat caliciviruses to bind histo-blood group antigens and overcome a significant barrier to cross-species transmission. Additionally, we have shown that bat norovirus maintains antigenic epitopes similar to those seen with human noroviruses, providing further evidence of evolutionary descent. Our results reiterate the importance of surveillance of wild-animal populations, especially of bats, for novel viral pathogens.IMPORTANCECaliciviruses are rapidly evolving viruses that cause pandemic outbreaks associated with significant morbidity and mortality globally. The animal reservoirs for human caliciviruses are unknown; bats represent critical reservoir species for several emerging and zoonotic diseases. Recent reports have identified several bat caliciviruses but have not characterized biological functions associated with disease risk, including their potential emergence in other mammalian populations. In this report, we identified a novel bat calicivirus that is most closely related to nonhuman primate caliciviruses. Using this new bat calicivirus and a second norovirus-like bat calicivirus capsid gene sequence, we generated virus-like particles that have host carbohydrate ligand binding patterns similar to those of human and animal noroviruses and that share antigens with human noroviruses. The similarities to human noroviruses with respect to binding patterns and antigenic epitopes illustrate the potential for bat caliciviruses to emerge in other species and the importance of pathogen surveillance in wild-animal populations.

scholarly journals Human Group C Rotavirus VP8*s Recognize Type A Histo-Blood Group Antigens as Ligands

2018 ◽  
Vol 92 (11) ◽  
Author(s):  
Xiaoman Sun ◽  
Lihong Wang ◽  
Jianxun Qi ◽  
Dandi Li ◽  
Mengxuan Wang ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Binding Site ◽  
Blood Group ◽  
Specific Interaction ◽  
Type A ◽  
Host Susceptibility ◽  
Structural Basis ◽  
Receptor Interaction ◽  
Blood Group Antigens ◽  
Group Species

ABSTRACTGroup/species C rotaviruses (RVCs) have been identified as important pathogens of acute gastroenteritis (AGE) in children, family-based outbreaks, as well as animal infections. However, little is known regarding their host-specific interaction, infection, and pathogenesis. In this study, we performed serial studies to characterize the function and structural features of a human G4P[2] RVC VP8* that is responsible for the host receptor interaction. Glycan microarrays demonstrated that the human RVC VP8* recognizes type A histo-blood group antigens (HBGAs), which was confirmed by synthetic glycan-/saliva-based binding assays and hemagglutination of red blood cells, establishing a paradigm of RVC VP8*-glycan interactions. Furthermore, the high-resolution crystal structure of the human RVC VP8* was solved, showing a typical galectin-like structure consisting of two β-sheets but with significant differences from cogent proteins of group A rotaviruses (RVAs). The VP8* in complex with a type A trisaccharide displays a novel ligand binding site that consists of a particular set of amino acid residues of the C-D, G-H, and K-L loops. RVC VP8* interacts with type A HBGAs through a unique mechanism compared with that used by RVAs. Our findings shed light on the host-virus interaction and the coevolution of RVCs and will facilitate the development of specific antivirals and vaccines.IMPORTANCEGroup/species C rotaviruses (RVCs), members ofReoviridaefamily, infect both humans and animals, but our knowledge about the host factors that control host susceptibility and specificity is rudimentary. In this work, we characterized the glycan binding specificity and structural basis of a human RVC that recognizes type A HBGAs. We found that human RVC VP8*, the rotavirus host ligand binding domain that shares only ∼15% homology with the VP8* domains of RVAs, recognizes type A HBGA at an as-yet-unknown glycan binding site through a mechanism distinct from that used by RVAs. Our new advancements provide insights into RVC-cell attachment, the critical step of virus infection, which will in turn help the development of control and prevention strategies against RVs.

scholarly journals Dual Recognition of Sialic Acid and αGal Epitopes by the VP8* Domains of the Bovine Rotavirus G6P[5] WC3 and of Its Mono-reassortant G4P[5] RotaTeq Vaccine Strains

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Mia Madel Alfajaro ◽  
Ji-Yun Kim ◽  
Laure Barbé ◽  
Eun-Hyo Cho ◽  
Jun-Gyu Park ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Blood Group ◽  
Intestinal Epithelial Cells ◽  
Sialic Acids ◽  
Blood Group Antigens ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Group A Rotaviruses ◽  
Group A ◽  
Small Intestinal

ABSTRACTGroup A rotaviruses, an important cause of severe diarrhea in children and young animals, initiate infection via interactions of the VP8* domain of the VP4 spike protein with cell surface sialic acids (SAs) or histo-blood group antigens (HBGAs). Although the bovine G6P[5] WC3 strain is an important animal pathogen and is also used in the bovine-human reassortant RotaTeq vaccine, the receptor(s) for the VP8* domain of WC3 and its reassortant strains have not yet been identified. In the present study, HBGA- and saliva-binding assays showed that both G6P[5] WC3 and mono-reassortant G4P[5] strains recognized the αGal HBGA. The infectivity of both P[5]-bearing strains was significantly reduced in αGal-free MA-104 cells by pretreatment with a broadly specific neuraminidase or by coincubation with the α2,6-linked SA-specificSambucus nigralectin, but not by the α2,3-linked specific sialidase or byMaackia amurensislectin. Free NeuAc and the αGal trisaccharide also prevented the infectivity of both strains. This indicated that both P[5]-bearing strains utilize α2,6-linked SA as a ligand on MA104 cells. However, the two strains replicated in differentiated bovine small intestinal enteroids and in their human counterparts that lack α2,6-linked SA or αGal HBGA, suggesting that additional or alternative receptors such as integrins, hsp70, and tight-junction proteins bound directly to the VP5* domain can be used by the P[5]-bearing strains to initiate the infection of human cells. In addition, these data also suggested that P[5]-bearing strains have potential for cross-species transmission.IMPORTANCEGroup A rotaviruses initiate infection through the binding of the VP8* domain of the VP4 protein to sialic acids (SAs) or histo-blood group antigens (HBGAs). Although the bovine G6P[5] WC3 strain is an important animal pathogen and is used as the backbone in the bovine-human reassortant RotaTeq vaccine, the receptor(s) for their P[5] VP8* domain has remained elusive. Using a variety of approaches, we demonstrated that the WC3 and bovine-human mono-reassortant G4P[5] vaccine strains recognize both α2,6-linked SA and αGal HBGA as ligands. Neither ligand is expressed on human small intestinal epithelial cells, explaining the absence of natural human infection by P[5]-bearing strains. However, we observed that the P[5]-bearing WC3 and G4P[5] RotaTeq vaccine strains could still infect human intestinal epithelial cells. Thus, the four P[5] RotaTeq vaccine strains potentially binding to additional alternative receptors may be efficient and effective in providing protection against severe rotavirus disease in human.

Association of Type 1 Blood Group Antigens with Urinary Tract Infections in Children with Genitourinary Structural Abnormalities

1990 ◽  
Vol 144 (2 Part 2) ◽  
pp. 469-473 ◽  
Author(s):  
Joel Sheinfeld ◽  
Carlos Cordon-Cardo ◽  
William R. Fair ◽  
David D. Wartinger ◽  
Ronald Rabinowitz
Keyword(s):  
Urinary Tract ◽  
Blood Group ◽  
Urinary Tract Infections ◽  
Blood Group Antigens ◽  
Structural Abnormalities ◽  
Tract Infections

Histo-blood group antigens: a common niche for norovirus and rotavirus

2014 ◽  
Vol 16 ◽  
Author(s):  
Ming Tan ◽  
Xi Jiang
Keyword(s):  
Helicobacter Pylori ◽  
Structural Analysis ◽  
Blood Group ◽  
Bacterial Pathogen ◽  
Binding Pocket ◽  
Lewis Antigens ◽  
Blood Group Antigens ◽  
Exploratory Research ◽  
Binding Interfaces ◽  
Selection Of

Noroviruses (NoVs) and rotaviruses (RVs), the two most important causes of viral acute gastroenteritis, are found to recognise histo-blood group antigens (HBGAs) as receptors or ligands for attachment. Human HBGAs are highly polymorphic containing ABO, secretor and Lewis antigens. In addition, both NoVs and RVs are highly diverse in how they recognise these HBGAs. Structural analysis of the HBGA-binding interfaces of NoVs revealed a conserved central binding pocket (CBP) interacting with a common major binding saccharide (MaBS) of HBGAs and a variable surrounding region interacting with additional minor binding saccharides. The conserved CBP indicates a strong selection of NoVs by the host HBGAs, whereas the variable surrounding region explains the diverse recognition patterns of different HBGAs by NoVs and RVs as functional adaptations of the viruses to human HBGAs. Diverse recognition of HBGAs has also been found in bacterial pathogenHelicobacter pylori. Thus, exploratory research into whether such diverse recognitions also occur for other viral and bacterial pathogens that recognise HBGAs is warranted.

The Distribution of Type 1 Chain ABH and Related Histo-Blood Group Antigens in Normal Cycling Human Endometrium

1993 ◽  
Vol 12 (1) ◽  
pp. 70-79 ◽  
Author(s):  
Vibeke Ravn ◽  
Christence Stubbe Teglbjaerg ◽  
Ulla Mandel ◽  
Erik Dabelsteen
Keyword(s):  
Blood Group ◽  
Human Endometrium ◽  
Blood Group Antigens

scholarly journals Molecular basis of P[6] and P[8] major human rotavirus VP8* domain interactions with histo-blood group antigens

2019 ◽  
Author(s):  
Shenyuan Xu ◽  
Yang Liu ◽  
Ming Tan ◽  
Weiming Zhong ◽  
Dandan Zhao ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Blood Group ◽  
Molecular Basis ◽  
Disease Burden ◽  
Binding Domain ◽  
Specific Cell ◽  
Blood Group Antigens ◽  
Nuclear Magnetic

AbstractInitial cell attachment of rotavirus (RV) to specific cell surface glycans, which is the essential first step in RV infection, is mediated by the VP8* domain of the spike protein VP4. Recently, human histo-blood group antigens (HBGAs) have been identified as ligands or receptors for human RV strains. RV strains in the P[4] and P[8] genotypes of the P[II] genogroup share common recognition of the Lewis b and H type 1 antigens, while P[6], which is one of the other genotypes in P[II], only recognizes the H type 1 antigen. The molecular basis of receptor recognition by the major human P[8] RVs remains unknown due to lack of experimental structural information. Here, we used nuclear magnetic resonance (NMR) titration experiments and NMR-derived high ambiguity driven docking (HADDOCK) methods to elucidate the molecular basis for P[8] VP8* recognition of the Leb and type 1 HBGAs and for P[6] recognition of H type 1 HBGAs. Unlike P[6] VP8* that recognizes H type 1 HGBAs in a binding surface composed of an α-helix and a β-sheet, referred as “βα binding domain”, the P[8] VP8* binds the type 1 HBGAs requiring the presence of the Lewis epitope in a previously undescribed pocket formed by two β-sheets, referred as “ββ binding domain”. The observation that P[6] and P[8] VP8* domains recognize different glycan structures at distinct binding sites supports the hypothesis that RV evolution is driven, at least in part, by selective pressure driven adaptation to HBGA structural diversity of their natural hosts living in the world. Recognition of the role that HBGAs play in driving RV evolution is essential to understanding RV diversity, host ranges, disease burden and zoonosis and to developing strategies to improve vaccines against RV infections.Author summaryRotaviruses (RV)s are the main cause of severe diarrhea in humans and animals. Significant advances in understanding RV diversity, evolution and epidemiology have been made after discovering that RVs recognize histo-blood group antigens (HBGAs) as host cell receptors. While different RV strains are known to have distinct binding preferences for HBGA receptors, the molecular basis in controlling strain-specific host ranges remains unclear. In this study, we used solution nuclear magnetic resonance to determine the molecular level details for interactions of the human P[8] and P[6] RV VP8* domains with their HBGA receptors. The distinct binding patterns observed between these major human RVs and their respective receptor ligands provides insight into the evolutionary relationships between different P[II] genotypes that ultimately determine host ranges, disease burden, zoonosis and epidemiology, which may impact future strategies for vaccine development against RVs.

scholarly journals Structural basis for antibody binding to adenylate cyclase toxin reveals RTX linkers as neutralization-sensitive epitopes

2021 ◽  
Vol 17 (9) ◽  
pp. e1009920
Author(s):  
Jory A. Goldsmith ◽  
Andrea M. DiVenere ◽  
Jennifer A. Maynard ◽  
Jason S. McLellan
Keyword(s):  
Adenylate Cyclase ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Structural Data ◽  
Antibody Binding ◽  
Structural Basis ◽  
Antibody Titers ◽  
Adenylate Cyclase Toxin ◽  
Blocking Antibodies

RTX leukotoxins are a diverse family of prokaryotic virulence factors that are secreted by the type 1 secretion system (T1SS) and target leukocytes to subvert host defenses. T1SS substrates all contain a C-terminal RTX domain that mediates recruitment to the T1SS and drives secretion via a Brownian ratchet mechanism. Neutralizing antibodies against the Bordetella pertussis adenylate cyclase toxin, an RTX leukotoxin essential for B. pertussis colonization, have been shown to target the RTX domain and prevent binding to the αMβ2 integrin receptor. Knowledge of the mechanisms by which antibodies bind and neutralize RTX leukotoxins is required to inform structure-based design of bacterial vaccines, however, no structural data are available for antibody binding to any T1SS substrate. Here, we determine the crystal structure of an engineered RTX domain fragment containing the αMβ2-binding site bound to two neutralizing antibodies. Notably, the receptor-blocking antibodies bind to the linker regions of RTX blocks I–III, suggesting they are key neutralization-sensitive sites within the RTX domain and are likely involved in binding the αMβ2 receptor. As the engineered RTX fragment contained these key epitopes, we assessed its immunogenicity in mice and showed that it elicits similar neutralizing antibody titers to the full RTX domain. The results from these studies will support the development of bacterial vaccines targeting RTX leukotoxins, as well as next-generation B. pertussis vaccines.

scholarly journals Structural Basis for Norovirus Inhibition by Human Milk Oligosaccharides

2016 ◽  
Vol 90 (9) ◽  
pp. 4843-4848 ◽  
Author(s):  
Stefan Weichert ◽  
Anna Koromyslova ◽  
Bishal K. Singh ◽  
Satoko Hansman ◽  
Stefan Jennewein ◽  
...  
Keyword(s):  
Human Milk ◽  
Blood Group ◽  
Structural Basis ◽  
Blood Group Antigens ◽  
Human Milk Oligosaccharides ◽  
Milk Oligosaccharides ◽  
X Ray ◽  
X Ray Crystallography ◽  
Naturally Occurring

Histo-blood group antigens (HBGAs) are important binding factors for norovirus infections. We show that two human milk oligosaccharides, 2′-fucosyllactose (2′FL) and 3-fucosyllactose (3FL), could block norovirus from binding to surrogate HBGA samples. We found that 2′FL and 3FL bound at the equivalent HBGA pockets on the norovirus capsid using X-ray crystallography. Our data revealed that 2′FL and 3FL structurally mimic HBGAs. These results suggest that 2′FL and 3FL might act as naturally occurring decoys in humans.

Sign in / Sign up

Export Citation Format

Share Document