Abstract

Noroviruses (NoVs), a group of single-stranded RNA viruses causing epidemic acute gastroenteritis in humans, are highly diverse, consisting of multiple genogroups with >30 genotypes. Their continual evolutions make NoV vaccine design and development difficult. Here, we report a study of NoV sequences obtained from a population-based diarrhea surveillance in Zhengding County of Hebei Province spanning from 2001 to 2019 and those available in the GenBank database from 1966 to 2019. NoV genotypes and/or variants that may evade immunity were screened and identified based on primary and conformational structures for vaccine design. We selected 366, 301, 139, 74 and 495 complete VP1-coding nucleotide sequences representing the predominant genotypes of GII.4, GII.2, GII.3, GII.6 and GII.17, respectively. A total of 16 distinct GII.4 variants were identified, showing a typical linear evolutionary pattern of variant replacement, while only 1–4 variants of the other genotypes were found to co-circulate over the 40–50-year period without typical variant replacement. The vaccine strain GII.4c is close to variant Sydney_2012 (0.053) in their primary structure, but they are distinct at epitopes A and E in conformations. Our data suggested GII.4 variant Sydney_2012, GII.2 variant A, a GII.3 strain, GII.6 variants B and C and GII.17 variant D are primary candidate strains for NoV vaccine development.

Highlights

  • Noroviruses (NoVs) are a common cause of acute gastroenteritis among young children worldwide [1]

  • To reveal the global temporal dynamics of NoVs, 26,469 NoV sequences with confirmed capsid types, including 362 from our population-based surveillance in Zhengding Country, and 26,107 available in the GenBank database were collected to analyze the prevalence of NoV genotypes during the past 50 years (Figure 1)

  • An unexpected prevalence increase of GII.2 was noted starting in 2016, and it has become the predominant genotype in recent years (2016–2019)

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Summary

Introduction

Noroviruses (NoVs) are a common cause of acute gastroenteritis among young children worldwide [1]. They are RNA viruses constituting the Norovirus genus in the family Caliciviridae. Each NoV virion is encapsulated by an icosahedral protein capsid containing a positive-sense, single-stranded RNA genome in ~7.7 kb with three open reading frames (ORFs) [2]. Structure studies revealed that VP1 has two major regions, a N-terminal shell (S) and a C-terminal protruding (P) domain. The latter is further divided into the moderately conservative P1 and the highly variable P2 subdomains [3,4]. In vitro expression of VP1 results in self-assembled virus-like particles (VLPs), being composed of 90 VP1 dimers

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