Characterization of Antigenic Relatedness between GII.4 and GII.17 Noroviruses by Use of Serum Samples from Norovirus-Infected Patients

Dai, Ying-Chun; Xia, Ming; Huang, Qiong; Tan, Ming; Lin, Qiang; Zhuang, Yuehong; Yan, Lei; Li, Jiandong; Jiang, Xi; Zhang, Xu-Fu

doi:10.1128/jcm.00865-17

Cited by 21 publications

(29 citation statements)

References 32 publications

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“…3), indicating their evolutionary changes over time. These differences may contribute to the observed antigenic differences among different GII.17 variants (33), as well as those between GII.17 huNoVs and other GII genotypes (41).…”

Section: Resultsmentioning

confidence: 99%

Structural Adaptations of Norovirus GII.17/13/21 Lineage through Two Distinct Evolutionary Paths

Qian

Song

Jiang

et al. 2019

J Virol

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Human noroviruses (huNoVs), which cause epidemic acute gastroenteritis, recognize histo-blood group antigens (HBGAs) as host attachment factors affecting host susceptibility. HuNoVs are genetically diverse, containing at least 31 genotypes in the two major genogroups (genogroup I [GI] and GII). Three GII genotypes, GII genotype 17 (GII.17), GII.13, and GII.21, form a unique genetic lineage, in which the GII.17 genotype retains the conventional GII HBGA binding site (HBS), while the GII.13/21 genotypes acquire a completely new HBS. To understand the molecular bases behind these evolutionary changes, we solved the crystal structures of the HBGA binding protruding domains of (i) an early GII.17 variant (the 1978 variant) that does not bind or binds weakly to HBGAs, (ii) the new GII.17 variant (the 2014/15 variant) that binds A/B/H antigens strongly via an optimized GII HBS, and (iii) a GII.13 variant (the 2010 variant) that binds the Lewis a (Lea) antigen via the new HBS. These serial, high-resolution structural data enable a comprehensive structural comparison to understand the evolutionary changes of the GII.17/13/21 lineage, including the emergence of the new HBS of the GII.13/21 sublineage and the possible HBS optimization of the recent GII.17 variant for an enhanced HBGA binding ability. Our study elucidates the structural adaptations of the GII.17/13/21 lineage through distinct evolutionary paths, which may allow a theory explaining huNoV adaptations and evolutions to be put forward. IMPORTANCE Our understanding of the molecular bases behind the interplays between human noroviruses and their host glycan ligands, as well as their evolutionary changes over time with alterations in their host ligand binding capability and host susceptibility, remains limited. By solving the crystal structures of the glycan ligand binding protruding (P) domains with or without glycan ligands of three representative noroviruses of the GII.17/13/21 genetic lineage, we elucidated the molecular bases of the human norovirus-glycan interactions of this special genetic lineage. We present solid evidence on how noroviruses of this genetic lineage evolved via different evolutionary paths to (i) optimize their glycan binding site for higher glycan binding function and (ii) acquire a completely new glycan binding site for new ligands. Our data shed light on the mechanism of the structural adaptations of human noroviruses through different evolutionary paths, facilitating our understanding of human norovirus adaptations, evolutions, and epidemiology.

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Section: Resultsmentioning

confidence: 99%

Structural Adaptations of Norovirus GII.17/13/21 Lineage through Two Distinct Evolutionary Paths

Qian

Song

Jiang

et al. 2019

J Virol

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“…The glycan binding profiles of huNoVs have been shown to be associated with their infection risk (3, 24–29), and possibly also their prevalence (19, 21). We showed that the GII.13/21 huNoVs with the new GBS recognize a broad spectrum of terminal β-Gal-containing glycans, including mucin core 2.…”

Section: Discussionmentioning

confidence: 99%

“…For example, a new variant of the previously rare genotype GII.17 became the predominant strain to cause outbreaks during the epidemic season of 2014–2015 (17, 18). Along with the antigenic change (17), the new GII.17 variant had a broader HBGA binding spectrum due to minor mutations at the conserved GII glycan binding site (GBS) (18–21). Therefore, identification of the new huNoV-glycan interactions, especially those of the rare genotypes, is necessary to help in the prevention and control of huNoV-associated diseases.…”

Section: Introductionmentioning

confidence: 99%

GII.13/21 Noroviruses Recognize Glycans with a Terminal β-Galactose via an Unconventional Glycan Binding Site

Sun

et al. 2019

J Virol

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Human noroviruses (huNoVs) recognize histo-blood group antigens (HBGAs) as host susceptibility factors. GII.13 and GII.21 huNoVs form a unique genetic lineage that emerged from mainstream GII NoVs via development of a new, nonconventional glycan binding site (GBS) that binds Lea antigen. This previous finding raised the question of whether the new GII.13/21 GBS really has such a narrow glycan binding spectrum. In this study, we provide solid phenotypic and structural evidence indicating that this new GBS recognizes a group of glycans with a common terminal β-galactose (β-Gal). First, we found that P domain proteins of GII.13/21 huNoVs circulating at different times bound three glycans sharing a common terminal β-Gal, including Lec, lactose, and mucin core 2. Second, we solved the crystal structures of the GII.13 P dimers in complex with Lec and mucin core 2, which showed that β-Gal is the major binding saccharide. Third, nonfat milk and lactose blocked the GII.13/21 P domain-glycan binding, which may explain the low prevalence of GII.13/21 viruses. Our data provide new insight into the host interactions and epidemiology of huNoVs, which would help in the control and prevention of NoV-associated diseases. IMPORTANCE Evidence from both phenotypic binding assay and structural study support the observed interactions of human noroviruses (huNoVs) with histo-blood group antigens (HBGAs) as receptors or attachment factors, affecting their host susceptibility. GII.13 and GII.21 genotypes form a unique genetic lineage that differs from the mainstream GII huNoVs in their unconventional glycan binding site. Unlike the previous findings that GII.13/21 genotypes recognize only Lea antigen, we found in this study that they can interact with a group of glycans with a common terminal β-Gal, including Lec, lactose, and mucin core 2. However, this wide glycan binding spectrum in a unique binding mode of the GII.13/21 huNoVs appears not to increase their prevalence, probably due to the existence of decoy glycan receptors in human gastrointestinal tract limiting their infection. Our findings shed light on the host interaction and epidemiology of huNoVs, which would impact the strategy of huNoV control and prevention.

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“…In contrast, NV conferred immunity to a later challenge with the Montgomery County virus (GI.5), suggesting an antigenic relatedness between genotypes within a genogroup (112). However, it is not always the case since by measuring cross-reactivity and cross-blockade activity, using serum samples from HuNoV-infected patients, limited crossreactivity was found but no cross-blockade activity between GII.4 and GII.17, suggesting that GII.4-specific immunity does not provide efficient protection against the GII.17 genotype (125).…”

Section: Humoral Immune Responsementioning

confidence: 99%

Human Norovirus Proteins: Implications in the Replicative Cycle, Pathogenesis, and the Host Immune Response

et al. 2020

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Human noroviruses (HuNoVs) are the cause of more than 95% of epidemic non-bacterial gastroenteritis worldwide, with some lethal cases. These viral agents affect people of all ages. However, young children and older adults are the highest-risk groups, being affected with the greatest rate of hospitalizations and morbidity cases. HuNoV structural proteins, especially VP1, have been studied extensively. In contrast, the functions of the non-structural proteins of the virus have been undescribed in depth. Studies on HuNoV non-structural proteins have mostly been made by expressing them individually in in vitro cultures, providing insights of their functions and the role that they play in HuNoV replication and pathogenesis. This review examines exhaustively the functions of both HuNoV structural and non-structural proteins and their possible role within the viral replicative cycle and the pathogenesis of the virus. It also highlights recent findings regarding the host's innate and adaptive immune responses against HuNoV, which are of great relevance for diagnostics and vaccine development so as to prevent infections caused by these fastidious viruses.

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Characterization of Antigenic Relatedness between GII.4 and GII.17 Noroviruses by Use of Serum Samples from Norovirus-Infected Patients

Cited by 21 publications

References 32 publications

Structural Adaptations of Norovirus GII.17/13/21 Lineage through Two Distinct Evolutionary Paths

Structural Adaptations of Norovirus GII.17/13/21 Lineage through Two Distinct Evolutionary Paths

GII.13/21 Noroviruses Recognize Glycans with a Terminal β-Galactose via an Unconventional Glycan Binding Site

Human Norovirus Proteins: Implications in the Replicative Cycle, Pathogenesis, and the Host Immune Response

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