Abstract
BackgroundHuman 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 FindingsHere 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/SignificanceOur 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.
Highlights
Noroviruses are the predominant aetiological agent of outbreaks of infectious gastroenteritis, and are typically associated with winter seasonality
In this paper we describe the amino acid variation observed in the P2 domain of a number of isolates of GII-4 noroviruses collected between 1997 and 2006, and which represent GII-4 variant strains circulating over a 9 year period in the UK
Homologous and/or non-homologous changes at aa hotspots that coincided with the epidemic waves and were located in exposed regions of the capsid structure were predicted to have a significant impact on the antigenic properties of the virus
Summary
Noroviruses are the predominant aetiological agent of outbreaks of infectious gastroenteritis, and are typically associated with winter seasonality. Outbreaks are mainly reported in hospitals and elderly care homes, but have been associated with other semi-closed environments such as schools, restaurants, cruise ships and hotels [1,2] Disease caused by these viruses is usually mild and selflimiting, which generally subsides 24–48 hours after onset. The second open reading frame, ORF2, encodes the major structural protein VP1, which has been shown to be organised into distinct domains [4] including a conserved shell (S) domain which forms the contiguous shell of the virus, and a protruding (P) domain which extends away from the capsid This protruding domain is organised into a highly variable P2 region which is flanked on either side by more conserved P1-1 and P1-2 domains. 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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