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Phylodynamic reconstruction reveals norovirus GII.4 epidemic expansions and their molecular determinants.

Siebenga JJ, Lemey P, Kosakovsky Pond SL, Rambaut A, Vennema H, Koopmans M - PLoS Pathog. (2010)

Bottom Line: The GII.4 strains included in our analyses evolved at a rate of 4.3-9.0x10(-3) mutations per site per year, and share a most recent common ancestor in the early 1980s.While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication.We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant.

View Article: PubMed Central - PubMed

Affiliation: National Institute for Public Health and the Environment, RIVM, Bilthoven, The Netherlands. joukjes@yahoo.co.uk

ABSTRACT
Noroviruses are the most common cause of viral gastroenteritis. An increase in the number of globally reported norovirus outbreaks was seen the past decade, especially for outbreaks caused by successive genogroup II genotype 4 (GII.4) variants. Whether this observed increase was due to an upswing in the number of infections, or to a surveillance artifact caused by heightened awareness and concomitant improved reporting, remained unclear. Therefore, we set out to study the population structure and changes thereof of GII.4 strains detected through systematic outbreak surveillance since the early 1990s. We collected 1383 partial polymerase and 194 full capsid GII.4 sequences. A Bayesian MCMC coalescent analysis revealed an increase in the number of GII.4 infections during the last decade. The GII.4 strains included in our analyses evolved at a rate of 4.3-9.0x10(-3) mutations per site per year, and share a most recent common ancestor in the early 1980s. Determinants of adaptation in the capsid protein were studied using different maximum likelihood approaches to identify sites subject to diversifying or directional selection and sites that co-evolved. While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication. We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant. While norovirus infections are generally mild and self-limiting, more severe outcomes of infection frequently occur in elderly and immunocompromized people, and no treatment is available. The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a cause for concern.

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Sites identified by molecular adaptation analyses located on top of the GII.4 capsid dimer.Two parts of the dimer were given different shades of blue, the sites identified as under positive selection, co-evolving with other sites, or sites previously identified to be involved in host-interactions, were colored yellow. Ligands (B trisaccaride) bound in the binding pocket are shown in red. Protein structure 2OBT was used for generating this representation [53].
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ppat-1000884-g005: Sites identified by molecular adaptation analyses located on top of the GII.4 capsid dimer.Two parts of the dimer were given different shades of blue, the sites identified as under positive selection, co-evolving with other sites, or sites previously identified to be involved in host-interactions, were colored yellow. Ligands (B trisaccaride) bound in the binding pocket are shown in red. Protein structure 2OBT was used for generating this representation [53].

Mentions: All sites for which molecular adaptation was detected are listed presented in Table 3. We marked relevant sites located on top of the capsid dimer in Figure 5.


Phylodynamic reconstruction reveals norovirus GII.4 epidemic expansions and their molecular determinants.

Siebenga JJ, Lemey P, Kosakovsky Pond SL, Rambaut A, Vennema H, Koopmans M - PLoS Pathog. (2010)

Sites identified by molecular adaptation analyses located on top of the GII.4 capsid dimer.Two parts of the dimer were given different shades of blue, the sites identified as under positive selection, co-evolving with other sites, or sites previously identified to be involved in host-interactions, were colored yellow. Ligands (B trisaccaride) bound in the binding pocket are shown in red. Protein structure 2OBT was used for generating this representation [53].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865530&req=5

ppat-1000884-g005: Sites identified by molecular adaptation analyses located on top of the GII.4 capsid dimer.Two parts of the dimer were given different shades of blue, the sites identified as under positive selection, co-evolving with other sites, or sites previously identified to be involved in host-interactions, were colored yellow. Ligands (B trisaccaride) bound in the binding pocket are shown in red. Protein structure 2OBT was used for generating this representation [53].
Mentions: All sites for which molecular adaptation was detected are listed presented in Table 3. We marked relevant sites located on top of the capsid dimer in Figure 5.

Bottom Line: The GII.4 strains included in our analyses evolved at a rate of 4.3-9.0x10(-3) mutations per site per year, and share a most recent common ancestor in the early 1980s.While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication.We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant.

View Article: PubMed Central - PubMed

Affiliation: National Institute for Public Health and the Environment, RIVM, Bilthoven, The Netherlands. joukjes@yahoo.co.uk

ABSTRACT
Noroviruses are the most common cause of viral gastroenteritis. An increase in the number of globally reported norovirus outbreaks was seen the past decade, especially for outbreaks caused by successive genogroup II genotype 4 (GII.4) variants. Whether this observed increase was due to an upswing in the number of infections, or to a surveillance artifact caused by heightened awareness and concomitant improved reporting, remained unclear. Therefore, we set out to study the population structure and changes thereof of GII.4 strains detected through systematic outbreak surveillance since the early 1990s. We collected 1383 partial polymerase and 194 full capsid GII.4 sequences. A Bayesian MCMC coalescent analysis revealed an increase in the number of GII.4 infections during the last decade. The GII.4 strains included in our analyses evolved at a rate of 4.3-9.0x10(-3) mutations per site per year, and share a most recent common ancestor in the early 1980s. Determinants of adaptation in the capsid protein were studied using different maximum likelihood approaches to identify sites subject to diversifying or directional selection and sites that co-evolved. While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication. We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant. While norovirus infections are generally mild and self-limiting, more severe outcomes of infection frequently occur in elderly and immunocompromized people, and no treatment is available. The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a cause for concern.

Show MeSH
Related in: MedlinePlus