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The recombinant origin of emerging human norovirus GII.4/2008: intra-genotypic exchange of the capsid P2 domain.

ABSTRACT: GII.4 noroviruses are a major cause of acute gastroenteritis in humans. A new variant of GII.4, the 2008 variant, has recently increased its prevalence on a global scale. A previous study of this variant in Japan suggested that it might be of recombinant origin, with a breakpoint at the ORF1-ORF2 junction. Here, examination of the evolutionary origin of the 2008 variant based on a larger sample of worldwide GII.4 norovirus sequences revealed a more complex pattern of recombination between the 2006a- and 2006b-like variants of genotype GII.4, involving the P2 antigenic domain. Double (termed '2008i') and triple (termed '2008ii') recombinant forms of 2008 variants were identified. This study highlights the possible importance of intra-genotypic recombination over antigenic regions in driving norovirus evolution, and is suggestive of a process analogous to the antigenic shift of influenza A virus by reassortment.

SUBMITTER: Lam TT

PROVIDER: S-EPMC7346602 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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The recombinant origin of emerging human norovirus GII.4/2008: intra-genotypic exchange of the capsid P2 domain.

Lam Tommy Tsan-Yuk TT Zhu Huachen H Smith David K DK Guan Yi Y Holmes Edward C EC Pybus Oliver G OG

The Journal of general virology 20120113 Pt 4

GII.4 noroviruses are a major cause of acute gastroenteritis in humans. A new variant of GII.4, the 2008 variant, has recently increased its prevalence on a global scale. A previous study of this variant in Japan suggested that it might be of recombinant origin, with a breakpoint at the ORF1-ORF2 junction. Here, examination of the evolutionary origin of the 2008 variant based on a larger sample of worldwide GII.4 norovirus sequences revealed a more complex pattern of recombination between the 20 ...[more]

PMID: 22238233

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Project description:Genotype II.3 (GII.3) noroviruses are a major cause of sporadic gastroenteritis, particularly in children. The greater incidence of GII.3 noroviruses in the pediatric population compared to the adult demographic suggests development of herd immunity to this genotype, possibly as a consequence of limited evolution of immune epitopes. This study aimed to identify and characterize immune epitopes on the GII.3 capsid protein and to determine the level of immune cross-reactivity within the genotype. A panel of seven GII.3 virus-like particles (VLPs), representing norovirus strains isolated during 1975 to 2008, was tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with human sera and a rabbit anti-GII.3 strain-specific polyclonal serum generated against the 2008 GII.3 VLP. Immunoprecipitation of protease-digested GII.3 VLPs and sequencing of bound peptides via mass spectrometry were used to locate epitopes on the capsid. Two epitopes were investigated further using Mimotopes technology. Serum binding studies demonstrated complete intragenotype GII.3 cross-reactivity using both human and rabbit serum. Six immunoreactive regions containing epitopes were located on the GII.3 capsid protein, two within each capsid domain. Epitopes in the S and P1 domains were highly conserved within GII.3 noroviruses. P2 domain epitopes were variable and contained evolutionarily important residues and histo-blood group antigen (HBGA) binding residues. In conclusion, anti-GII.3 antibody-binding epitopes are highly cross-reactive and mostly conserved within GII.3 strains. This may account for the limited GII.3 prevalence in adults and suggests that a GII.3 strain may be a valuable inclusion in a multivalent pediatric targeted VLP vaccine. Exploration of norovirus immune epitopes is vital for effective vaccine design. IMPORTANCE This study represents an important contribution to the understanding of norovirus immunology in a pediatric genotype. The high cross-reactivity and conservation of GII.3 epitopes suggest development of herd immunity against GII.3 and indicate that a GII.3 strain would be a valuable inclusion in a pediatric targeted multivalent vaccine. Immunological understanding of pediatric norovirus strains is important since norovirus vaccines will likely target high-risk groups such as the pediatric population.

Project description:BackgroundWith the help of an existing citywide comprehensive surveillance on gastroenteritis outpatients, although norovirus genogroup II (NoV GII) was tested routinely, its genotypes were never investigated systematically on a municipal level. This study aimed to understand the prevalence, major genotypes and evolutional trends of NoV GII in Shanghai during the period of 2016-2018, and to provide molecular bases for early warning for any potential NoV outbreaks.Methods27 sentinel hospitals from all 16 districts were recruited by stratified probability proportional to size (PPS) method in Shanghai comprehensive diarrhea surveillance programme. Stool samples were collected and screened for NoV GII by real-time reverse transcription polymerase chain reaction (qRT-PCR). For samples that were positive in qRT-PCR, conventional RT-PCR was performed to amplify the ORF1-ORF2 junction of NoV GII gene. Generated sequences were typed by RIVM online genotyping tool, and then strains of interest were analyzed phylogenetically using MEGA 6.0.ResultsA total of 7883 stool samples were collected from diarrhea outpatients, among which 6474 were from adults and 1409 were from children. 13.66% (1077 cases) were screened positive in qRT-PCR for NoV GII, from which 71.96% (775 cases) were sequenced successfully. The top three genotypes were GII.Pe/GII.4 (37%), GII.P17/GII.17 (26%) and GII.P16/GII.2 (17%). While GII.Pe/GII.4 detection rate decreased significantly over the 3 years (from 48.4 to 20.9%); GII.P16/GII.2 appeared for the first time in October 2016 and rose rapidly to 27.0% in 2017, but fell back to 23.4% in 2018. Meanwhile there was a significant increase for both GII.P12/GII.3 and GII.P7/GII.6 recombinant genotypes detected in adult population in 2018. Phylogenic analysis revealed the existence of multiple gene clusters within both of these recombinant genotypes.ConclusionUnlike the alternating circulation of GII.4 and non-GII.4 NoV observed in 2016 or 2017, the genotype profile of NoV GII in 2018 was characterized by the co-prevalence of multiple recombinant genotypes. A recent increase in detection rate in less reported recombinant genotypes such as GII.P12/GII.3 and GII.P7/GII.6 among adult population calls for a continuing close monitoring on NoV GII genotypes in case of potential local outbreaks.

Dataset Information

The recombinant origin of emerging human norovirus GII.4/2008: intra-genotypic exchange of the capsid P2 domain.

Publications

The recombinant origin of emerging human norovirus GII.4/2008: intra-genotypic exchange of the capsid P2 domain.

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