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)
Summary
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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