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Analysis of amino acid variation in the P2 domain of the GII-4 norovirus VP1 protein reveals putative variant-specific epitopes.

Allen DJ, Gray JJ, Gallimore CI, Xerry J, Iturriza-Gómara M - PLoS ONE (2008)

Bottom Line: Our data identifies two sites in this region, which show significant amino acid substitutions associated with the appearance of variant strains responsible for epidemics with major public health impact.Homology modelling studies revealed the exposed nature of these sites on the capsid surface, providing supportive structural data that these two sites are likely to be associated with putative variant-specific epitopes.Furthermore, the patterns in the evolution of these viruses at these sites suggests that noroviruses follow a neutral network pattern of evolution.

View Article: PubMed Central - PubMed

Affiliation: Enteric Virus Unit, Virus Reference Department, Centre For Infections, Health Protection Agency, London, United Kingdom. david.james.allen@hpa.org.uk

ABSTRACT

Background: Human noroviruses are a highly diverse group of viruses classified into three of the five currently recognised Norovirus genogroups, and contain numerous genotypes or genetic clusters. Noroviruses are the major aetiological agent of endemic gastroenteritis in all age groups, as well as the cause of periodic epidemic gastroenteritis. The noroviruses most commonly associated with outbreaks of gastroenteritis are genogroup II genotype 4 (GII-4) strains. The relationship between genotypes of noroviruses with their phenotypes and antigenic profile remains poorly understood through an inability to culture these viruses and the lack of a suitable animal model.

Methodology/principal findings: Here we describe a study of the diversity of amino acid sequences of the highly variable P2 region in the major capsid protein, VP1, of the GII-4 human noroviruses strains using sequence analysis and homology modelling techniques.

Conclusions/significance: Our data identifies two sites in this region, which show significant amino acid substitutions associated with the appearance of variant strains responsible for epidemics with major public health impact. Homology modelling studies revealed the exposed nature of these sites on the capsid surface, providing supportive structural data that these two sites are likely to be associated with putative variant-specific epitopes. Furthermore, the patterns in the evolution of these viruses at these sites suggests that noroviruses follow a neutral network pattern of evolution.

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Related in: MedlinePlus

Phylogenetic tree based on nt data showing 66 GII-4 norovirus sequences used in this study.Values indicate significant bootstrap values (1000 pseudoreplicates) that define lineages. Genetic lineages marked on the right (I–IV). Dates indicate the year of isolation
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pone-0001485-g001: Phylogenetic tree based on nt data showing 66 GII-4 norovirus sequences used in this study.Values indicate significant bootstrap values (1000 pseudoreplicates) that define lineages. Genetic lineages marked on the right (I–IV). Dates indicate the year of isolation

Mentions: Nucleotide data for 66 P2 domain sequences revealed significant diversity of up to 20% across this region. Analysis of the sequences by the neighbour joining method followed by bootstrap analysis (1000 pseudoreplicates) revealed four genetic lineages defined by bootstrap values ≥99%, Figure 1.


Analysis of amino acid variation in the P2 domain of the GII-4 norovirus VP1 protein reveals putative variant-specific epitopes.

Allen DJ, Gray JJ, Gallimore CI, Xerry J, Iturriza-Gómara M - PLoS ONE (2008)

Phylogenetic tree based on nt data showing 66 GII-4 norovirus sequences used in this study.Values indicate significant bootstrap values (1000 pseudoreplicates) that define lineages. Genetic lineages marked on the right (I–IV). Dates indicate the year of isolation
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2194622&req=5

pone-0001485-g001: Phylogenetic tree based on nt data showing 66 GII-4 norovirus sequences used in this study.Values indicate significant bootstrap values (1000 pseudoreplicates) that define lineages. Genetic lineages marked on the right (I–IV). Dates indicate the year of isolation
Mentions: Nucleotide data for 66 P2 domain sequences revealed significant diversity of up to 20% across this region. Analysis of the sequences by the neighbour joining method followed by bootstrap analysis (1000 pseudoreplicates) revealed four genetic lineages defined by bootstrap values ≥99%, Figure 1.

Bottom Line: Our data identifies two sites in this region, which show significant amino acid substitutions associated with the appearance of variant strains responsible for epidemics with major public health impact.Homology modelling studies revealed the exposed nature of these sites on the capsid surface, providing supportive structural data that these two sites are likely to be associated with putative variant-specific epitopes.Furthermore, the patterns in the evolution of these viruses at these sites suggests that noroviruses follow a neutral network pattern of evolution.

View Article: PubMed Central - PubMed

Affiliation: Enteric Virus Unit, Virus Reference Department, Centre For Infections, Health Protection Agency, London, United Kingdom. david.james.allen@hpa.org.uk

ABSTRACT

Background: Human noroviruses are a highly diverse group of viruses classified into three of the five currently recognised Norovirus genogroups, and contain numerous genotypes or genetic clusters. Noroviruses are the major aetiological agent of endemic gastroenteritis in all age groups, as well as the cause of periodic epidemic gastroenteritis. The noroviruses most commonly associated with outbreaks of gastroenteritis are genogroup II genotype 4 (GII-4) strains. The relationship between genotypes of noroviruses with their phenotypes and antigenic profile remains poorly understood through an inability to culture these viruses and the lack of a suitable animal model.

Methodology/principal findings: Here we describe a study of the diversity of amino acid sequences of the highly variable P2 region in the major capsid protein, VP1, of the GII-4 human noroviruses strains using sequence analysis and homology modelling techniques.

Conclusions/significance: Our data identifies two sites in this region, which show significant amino acid substitutions associated with the appearance of variant strains responsible for epidemics with major public health impact. Homology modelling studies revealed the exposed nature of these sites on the capsid surface, providing supportive structural data that these two sites are likely to be associated with putative variant-specific epitopes. Furthermore, the patterns in the evolution of these viruses at these sites suggests that noroviruses follow a neutral network pattern of evolution.

Show MeSH
Related in: MedlinePlus