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. 2020 Dec 8:11:607723.
doi: 10.3389/fmicb.2020.607723. eCollection 2020.

Characterization of Antigenic Relatedness Among GI Norovirus Genotypes Using Serum Samples From Norovirus-Infected Patients and Mouse Sera

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Characterization of Antigenic Relatedness Among GI Norovirus Genotypes Using Serum Samples From Norovirus-Infected Patients and Mouse Sera

Dongjie Xie et al. Front Microbiol. .

Abstract

Characterizing diversity and the antigenic relatedness of norovirus remains a primary focus in understanding its biological properties and vaccine designs. The precise antigenic and serological features of GI genotypes have not been studied. The study represented an investigation on a gastroenteritis outbreak related to GI.3 norovirus and the three most detected GI genotypes, GI.2 (belonging to immunotype B), GI.3 and GI.9 (belonging to immunotype C), were selected to characterize their phylogenetic relationship, HBGA binding profiles and antigenic relatedness within (intra-immunotype), and between (inter-immunotypes) genotypes using mouse sera and patient's serum samples from the GI.3 related outbreak. Wide HBGA binding profiles and evolution of binding affinity were observed in the three GI genotypes studied. A low specific blockade antibody to GI.3 in the population generated the pool of susceptible individuals and supported virus spread in the outbreak. We found strong blockade immune response in homologous strains, moderate intra-immunotype blockade but weak inter-immunotypes blockade in humans following GI.3 norovirus infections. These findings further support the immunotypes grouping and will be valuable for optimizing the design of norovirus vaccine.

Keywords: GI genotypes; HBGA; cross-blockade; cross-reactivity; immunotypes; norovirus; vaccine strategy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Phylogenetic tree analyses based on nucleotide sequences encoding capsid NS terminus of the outbreak strains (330 bp fragment) (A) and P domain (B). The sequences used to express P proteins in this study were marked with pentagram. The bootstrap values generated from 1,000 replicates are shown at each node.
FIGURE 2
FIGURE 2
Comparisons of HBGA binding interfaces in green and the surrounding regions in blue of GI.2, GI.3, and GI.9 noroviruses. Substitutions of amino acid are shown in red.
FIGURE 3
FIGURE 3
HBGA binding profiles of GI.2 (A), GI.3 (B), and GI.9 (C) P proteins to saliva samples. A panel of saliva samples with confirmed phenotypes were used for HBGA binding profiles (Zhang et al., 2015). The binding signals are determined by optical density (Y axis). At the same time, the well-characterized saliva samples of volunteers (V as abbreviated for volunteers) are shown in X-axis. Various A, B, AB, O, and N stand for blood type A, B, AB, O, and non-secretor, respectively.
FIGURE 4
FIGURE 4
IgG titers (A) and blockade titers (B) to GI.2, GI.3, and GI.9 of the immunized mouse sera. The y-axis indicates the specific antibody titer (A) and blockade titer (B). The blue, orange, and purple bars indicate the mouse antiserum of GI.2, GI.3, and GI.9, respectively.
FIGURE 5
FIGURE 5
Serologic responses of IgG titers to GI.2, GI.3, and GI.9 of the paired human sera collected from the GI.3-related outbreak. Distribution of IgG titers at the acute phase (A), convalescent phase (B), and serological fold rises (C) among 21 individuals. The blue, orange, and purple bars indicate serologic responses to GI.2, GI.3, and GI.9, respectively.
FIGURE 6
FIGURE 6
Serologic responses of blockade titers to GI.2, GI.3, and GI.9 of the paired human sera collected from the GI.3-related outbreak. Distribution of blockade titers at the acute phase (A), convalescent phase (B), and serological fold rises (C) among 16 individuals with IgG seroconversion. The blue, orange, and purple bars indicate serologic responses to GI.2, GI.3, and GI.9, respectively.

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