Structural basis of host ligand specificity change of GII porcine noroviruses from their closely related GII human noroviruses

Yang, Yang; Xia, Ming; Wang, Leyi; Arumugam, Sahaana; Wang, Yajing; Ou, Xianjin; Wang, Chenlong; Jiang, Xi; Tan, Ming; Li, Xuemei

doi:10.1080/22221751.2019.1686335

Cited by 5 publications

(6 citation statements)

References 57 publications

(92 reference statements)

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“…Some of the other animal genotypes have been tested before, and the lack of attachment was expected. These include GIV.2 and GII.11 and GII.19, which did not attach to HBGAs or human saliva, respectively (54)(55)(56). Interestingly, the porcine genotypes have the conserved binding site, but no attachment factor has been identified yet.…”

Section: Discussionmentioning

confidence: 99%

Human Noroviruses Attach to Intestinal Tissues of a Broad Range of Animal Species

Villabruna

Schapendonk

Aron

et al. 2021

J Virol

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Human noroviruses are the most common non-bacterial cause of gastroenteritis outbreaks with new variants and genotypes frequently emerging. The origin of these new viruses is unknown; however, animals have been proposed as a potential source as human noroviruses have been detected in animal species. Here we investigated the potential of animals to serve as reservoir of human noroviruses, by testing noroviruses attachment to formalin-fixed intestinal tissues of a range of potential reservoir animals. We set up a novel method to study norovirus binding using fluorescein isothiocyanate (FITC)-labelled virus-like particles. In humans, noroviruses interact with histo-blood group antigens (HBGAs), carbohydrates that are expressed, among others, on the epithelial lining of the gastrointestinal tract. In animals, this interaction is not well understood. To test if virus binding depends on HBGAs, we characterized the HBGA phenotype in animal tissues by immunohistochemistry. With the exception of the black-headed gull and the straw-coloured fruitbat, we observed attachment of several human norovirus genotypes to the intestinal epithelium of all tested animal species. We did, however, not find an association between the expression of a specific HBGA phenotype and VLP attachment. We show that selected human noroviruses can attach to small intestinal tissues across species, supporting the hypothesis that human noroviruses could reside in an animal reservoir. However, whether this attachment can subsequently lead to infection, needs to be further assessed. IMPORTANCE Noroviruses are a major cause of acute gastroenteritis in humans. New norovirus variants and recombinants (re-)emerge regularly in the human population. From animal experiments and surveillance studies it has become clear that at least seven animal models are susceptible to infection with human strains and that domesticated and wild animals shed human noroviruses in their faeces. As virus attachment is a first important step for infection we used a novel method utilising FITC-labelled VLPs to test for norovirus attachment to intestinal tissues of potential animal hosts. We further characterized these tissues with regards to their HBGA expression, a well-studied norovirus susceptibility factor in humans. We found attachment of several human strains to a variety of animal species independent of their HBGA phenotype. This supports the hypothesis that human strains could reside in an animal reservoir.

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Section: Discussionmentioning

confidence: 99%

Human Noroviruses Attach to Intestinal Tissues of a Broad Range of Animal Species

Villabruna

Schapendonk

Aron

et al. 2021

J Virol

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“…The cDNA fragments encoding the P proteins of two clinical GI.3 huNoVs, the Desert Shield virus DSV395 (GenBank code: U04469.1 , VP1 amino acids 227–544) and the VA98115/1998 (GenBank code: AY038598.1 , VP1 amino acid 227–538), were chemically synthesized and cloned into expression vector pGEX-6P-1 at EcoRI and SalI / XhoI restriction sites. The P proteins were expressed in E. coli BL21(DE3) as described elsewhere ( 47 – 49 ). The resulting GST-P fusion proteins were purified using glutathione-Sepharose 4B (GE Healthcare Life Sciences) according to the manufacturer’s instructions, and the GST tag was removed with Prescission protease at 4°C overnight.…”

Section: Methodsmentioning

confidence: 99%

Structural Insight into Terminal Galactose Recognition by Two Non-HBGA Binding GI.3 Noroviruses

Wang

Kang

Tan

et al. 2022

J Virol

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“…A recent structural study has defined the HBGA binding site on the GII.3 strain TV24 (GenBank code: U02030) P domain, which is shaped primarily by eight residues including T357, R358, K363, D386, D388, S449, G451, and R452 [36]. These eight residues are identical among the TV24 strain (cluster 1) and the four GII.3 strains tested here (data not shown), suggesting that GII.3 maintains a conserved HBGA binding site despite the virus undergoing steady evolution.…”

Section: Structural Modeling Of the 8c7 And 8d1 Epitopesmentioning

confidence: 99%

“…The GII.3 VP1 protein can self-assemble into virus-like particles [34][35][36], with the outer P domain in either "resting" or "rising" conformation depending on the pH of sample solutions [35]. GII.3 VLPs formed by the entire VP1 protein or P particles solely made of the P domain can bind HBGAs in vitro [8,21,34,37].…”

Section: Introductionmentioning

confidence: 99%

“…GII.3 VLPs formed by the entire VP1 protein or P particles solely made of the P domain can bind HBGAs in vitro [8,21,34,37]. A recent structural study has defined an HBGA binding site on GII.3, which is constituted by eight VP1 residues within the P2 subdomain [36]. Immunization of animals with GII.3 VLPs elicited antibodies capable of blocking the interaction between HBGAs and homotypic VLPs [34,37], indicating that the GII.3 VP1 protein does contain blockade antibody epitopes.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

Wang

et al. 2021

Viruses

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Human noroviruses are a common pathogen causing acute gastroenteritis worldwide. Among all norovirus genotypes, GII.3 is particularly prevalent in the pediatric population. Here we report the identification of two distinct blockade antibody epitopes on the GII.3 capsid. We generated a panel of monoclonal antibodies (mAbs) from mice immunized with virus-like particle (VLP) of a GII.3 cluster 3 strain. Two of these mAbs, namely 8C7 and 8D1, specifically bound the parental GII.3 VLP but not VLPs of GII.4, GII.17, or GI.1. In addition, 8C7 and 8D1 efficiently blocked GII.3 VLP binding with its ligand, histo-blood group antigens (HBGA). These data demonstrate that 8C7 and 8D1 are GII.3-specific blockade antibodies. By using a series of chimeric VLPs, we mapped the epitopes of 8C7 and 8D1 to residues 385–400 and 401–420 of the VP1 capsid protein, respectively. These two blockade antibody epitopes are highly conserved among GII.3 cluster 3 strains. Structural modeling shows that the 8C7 epitope partially overlaps with the HBGA binding site (HBS) while the 8D1 epitope is spatially adjacent to HBS. These findings may enhance our understanding of the immunology and evolution of GII.3 noroviruses.

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Structural basis of host ligand specificity change of GII porcine noroviruses from their closely related GII human noroviruses

Cited by 5 publications

References 57 publications

Human Noroviruses Attach to Intestinal Tissues of a Broad Range of Animal Species

Human Noroviruses Attach to Intestinal Tissues of a Broad Range of Animal Species

Structural Insight into Terminal Galactose Recognition by Two Non-HBGA Binding GI.3 Noroviruses

Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

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