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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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Related in: MedlinePlus

Sites identified by Bayesian graphical models to co-evolve.Amino acid sites 297, 372, 368, 394, 407, 534 and 540 of the GII.4 capsid protein were depicted as trees showing different amino acids in different colors. Each connection is associated with posterior probabilities (P) for single (above or left) or two (below or right) dependencies.
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ppat-1000884-g004: Sites identified by Bayesian graphical models to co-evolve.Amino acid sites 297, 372, 368, 394, 407, 534 and 540 of the GII.4 capsid protein were depicted as trees showing different amino acids in different colors. Each connection is associated with posterior probabilities (P) for single (above or left) or two (below or right) dependencies.

Mentions: In folded proteins amino acids are not arranged linearly; many functionally interact, making their evolution dependant on that of others. Various types of interactions exist, and interacting sites are not necessarily direct neighbors in either the protein sequence or in the 3D protein structure. We used Bayesian graphical models (BGM) to detect co-evolving sites. The sites identified, are shown as a network in Figure 4, and sites for which co-evolution was detected but seemed less supported are shown in Figures S3A and S3B. Two values for the posterior probabilities are given, obtained from the analyses allowing for either one or two co-dependencies. Sites 231 and 209, and 238 and 504, which co-evolved as two coupled sets (Figures S3A and S3B), were not involved in recent variant transitions. Therefore we conclude that they were not under selective pressure that governed variant replacement dynamics.


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 Bayesian graphical models to co-evolve.Amino acid sites 297, 372, 368, 394, 407, 534 and 540 of the GII.4 capsid protein were depicted as trees showing different amino acids in different colors. Each connection is associated with posterior probabilities (P) for single (above or left) or two (below or right) dependencies.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1000884-g004: Sites identified by Bayesian graphical models to co-evolve.Amino acid sites 297, 372, 368, 394, 407, 534 and 540 of the GII.4 capsid protein were depicted as trees showing different amino acids in different colors. Each connection is associated with posterior probabilities (P) for single (above or left) or two (below or right) dependencies.
Mentions: In folded proteins amino acids are not arranged linearly; many functionally interact, making their evolution dependant on that of others. Various types of interactions exist, and interacting sites are not necessarily direct neighbors in either the protein sequence or in the 3D protein structure. We used Bayesian graphical models (BGM) to detect co-evolving sites. The sites identified, are shown as a network in Figure 4, and sites for which co-evolution was detected but seemed less supported are shown in Figures S3A and S3B. Two values for the posterior probabilities are given, obtained from the analyses allowing for either one or two co-dependencies. Sites 231 and 209, and 238 and 504, which co-evolved as two coupled sets (Figures S3A and S3B), were not involved in recent variant transitions. Therefore we conclude that they were not under selective pressure that governed variant replacement dynamics.

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