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Sequencing and analysis of globally obtained human respiratory syncytial virus A and B genomes.

Bose ME, He J, Shrivastava S, Nelson MI, Bera J, Halpin RA, Town CD, Lorenzi HA, Noyola DE, Falcone V, Gerna G, De Beenhouwer H, Videla C, Kok T, Venter M, Williams JV, Henrickson KJ - PLoS ONE (2015)

Bottom Line: We found multiple clades co-circulating globally for both RSV A and B.However, the distribution of clades can change rapidly as new strains emerge.We did not observe a strong spatial structure in our trees, with the same three main clades of RSV co-circulating globally, suggesting that the evolution of RSV is not strongly regionalized.

View Article: PubMed Central - PubMed

Affiliation: Midwest Respiratory Virus Program, Medical College of Wisconsin, Milwaukee, WI, USA.

ABSTRACT

Background: Human respiratory syncytial virus (RSV) is the leading cause of respiratory tract infections in children globally, with nearly all children experiencing at least one infection by the age of two. Partial sequencing of the attachment glycoprotein gene is conducted routinely for genotyping, but relatively few whole genome sequences are available for RSV. The goal of our study was to sequence the genomes of RSV strains collected from multiple countries to further understand the global diversity of RSV at a whole-genome level.

Methods: We collected RSV samples and isolates from Mexico, Argentina, Belgium, Italy, Germany, Australia, South Africa, and the USA from the years 1998-2010. Both Sanger and next-generation sequencing with the Illumina and 454 platforms were used to sequence the whole genomes of RSV A and B. Phylogenetic analyses were performed using the Bayesian and maximum likelihood methods of phylogenetic inference.

Results: We sequenced the genomes of 34 RSVA and 23 RSVB viruses. Phylogenetic analysis showed that the RSVA genome evolves at an estimated rate of 6.72 × 10(-4) substitutions/site/year (95% HPD 5.61 × 10(-4) to 7.6 × 10(-4)) and for RSVB the evolutionary rate was 7.69 × 10(-4) substitutions/site/year (95% HPD 6.81 × 10(-4) to 8.62 × 10(-4)). We found multiple clades co-circulating globally for both RSV A and B. The predominant clades were GA2 and GA5 for RSVA and BA for RSVB.

Conclusions: Our analyses showed that RSV circulates on a global scale with the same predominant clades of viruses being found in countries around the world. However, the distribution of clades can change rapidly as new strains emerge. We did not observe a strong spatial structure in our trees, with the same three main clades of RSV co-circulating globally, suggesting that the evolution of RSV is not strongly regionalized.

No MeSH data available.


Related in: MedlinePlus

G Protein Entropy Plot and Positive Selected Sites.This is an entropy plot of the G protein sequences with positively selected sites also shown. Entropy values were calculated using BioEdit 7.0 from the alignments used for the positive selection analysis and the plot was generated using Microsoft Excel. Black bars are for RSVA sequences and red bars are for RSVB sequences. Sites predicted to be under positive selection in this study are shown with black diamonds for RSVA and red diamonds for RSVB. Near the top are shown sites predicted to be under positive selection or diversifying selection from previously published studies with black pluses for RSVA and red pluses for RSVB.
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pone.0120098.g002: G Protein Entropy Plot and Positive Selected Sites.This is an entropy plot of the G protein sequences with positively selected sites also shown. Entropy values were calculated using BioEdit 7.0 from the alignments used for the positive selection analysis and the plot was generated using Microsoft Excel. Black bars are for RSVA sequences and red bars are for RSVB sequences. Sites predicted to be under positive selection in this study are shown with black diamonds for RSVA and red diamonds for RSVB. Near the top are shown sites predicted to be under positive selection or diversifying selection from previously published studies with black pluses for RSVA and red pluses for RSVB.

Mentions: We reviewed seven previously published studies to identify which sites have previously been predicted to be under positive selection [24,33,35–39]. Most of these studies focused on the G CDS, and the majority of the positively selected sites identified in this study were also identified in one or more of the previous studies (8/10 for RSVA and 2/4 for RSVB). Across all studies most of the sites predicted to be under positive selection were identified in only one study (60% for RSVA and 74% for RSVB). Differences between studies can be attributed to differences in data sets, prediction algorithms, and cutoff criteria used. However, like the previous studies most of the positively selected sites were identified in the highly variable mucin-like regions of the G gene (Fig. 2). It has previously been demonstrated that both humans and rabbits produce antibodies to these highly variable regions [40,41]. One of these studies used linear peptides representing natural amino acid variations in the carboxy-terminal mucin-like region of the G protein to demonstrate that human serum can contain antibodies to these regions of the protein and that even a single mutation can eliminate reactivity [41]. Additionally, reactivity of the serum with the peptides was dependent on the genotype of the RSV virus that infected the individual, and a mutation in one of the predicted positively selected sites (position 244 in M74568) was found to produce an antibody escape mutant [41]. Taken together these results support the concept that immunologic pressure is driving selection of mutations in these regions and that mutations in these regions play a role in the ability of RSV to re-infect individuals throughout their lives.


Sequencing and analysis of globally obtained human respiratory syncytial virus A and B genomes.

Bose ME, He J, Shrivastava S, Nelson MI, Bera J, Halpin RA, Town CD, Lorenzi HA, Noyola DE, Falcone V, Gerna G, De Beenhouwer H, Videla C, Kok T, Venter M, Williams JV, Henrickson KJ - PLoS ONE (2015)

G Protein Entropy Plot and Positive Selected Sites.This is an entropy plot of the G protein sequences with positively selected sites also shown. Entropy values were calculated using BioEdit 7.0 from the alignments used for the positive selection analysis and the plot was generated using Microsoft Excel. Black bars are for RSVA sequences and red bars are for RSVB sequences. Sites predicted to be under positive selection in this study are shown with black diamonds for RSVA and red diamonds for RSVB. Near the top are shown sites predicted to be under positive selection or diversifying selection from previously published studies with black pluses for RSVA and red pluses for RSVB.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368745&req=5

pone.0120098.g002: G Protein Entropy Plot and Positive Selected Sites.This is an entropy plot of the G protein sequences with positively selected sites also shown. Entropy values were calculated using BioEdit 7.0 from the alignments used for the positive selection analysis and the plot was generated using Microsoft Excel. Black bars are for RSVA sequences and red bars are for RSVB sequences. Sites predicted to be under positive selection in this study are shown with black diamonds for RSVA and red diamonds for RSVB. Near the top are shown sites predicted to be under positive selection or diversifying selection from previously published studies with black pluses for RSVA and red pluses for RSVB.
Mentions: We reviewed seven previously published studies to identify which sites have previously been predicted to be under positive selection [24,33,35–39]. Most of these studies focused on the G CDS, and the majority of the positively selected sites identified in this study were also identified in one or more of the previous studies (8/10 for RSVA and 2/4 for RSVB). Across all studies most of the sites predicted to be under positive selection were identified in only one study (60% for RSVA and 74% for RSVB). Differences between studies can be attributed to differences in data sets, prediction algorithms, and cutoff criteria used. However, like the previous studies most of the positively selected sites were identified in the highly variable mucin-like regions of the G gene (Fig. 2). It has previously been demonstrated that both humans and rabbits produce antibodies to these highly variable regions [40,41]. One of these studies used linear peptides representing natural amino acid variations in the carboxy-terminal mucin-like region of the G protein to demonstrate that human serum can contain antibodies to these regions of the protein and that even a single mutation can eliminate reactivity [41]. Additionally, reactivity of the serum with the peptides was dependent on the genotype of the RSV virus that infected the individual, and a mutation in one of the predicted positively selected sites (position 244 in M74568) was found to produce an antibody escape mutant [41]. Taken together these results support the concept that immunologic pressure is driving selection of mutations in these regions and that mutations in these regions play a role in the ability of RSV to re-infect individuals throughout their lives.

Bottom Line: We found multiple clades co-circulating globally for both RSV A and B.However, the distribution of clades can change rapidly as new strains emerge.We did not observe a strong spatial structure in our trees, with the same three main clades of RSV co-circulating globally, suggesting that the evolution of RSV is not strongly regionalized.

View Article: PubMed Central - PubMed

Affiliation: Midwest Respiratory Virus Program, Medical College of Wisconsin, Milwaukee, WI, USA.

ABSTRACT

Background: Human respiratory syncytial virus (RSV) is the leading cause of respiratory tract infections in children globally, with nearly all children experiencing at least one infection by the age of two. Partial sequencing of the attachment glycoprotein gene is conducted routinely for genotyping, but relatively few whole genome sequences are available for RSV. The goal of our study was to sequence the genomes of RSV strains collected from multiple countries to further understand the global diversity of RSV at a whole-genome level.

Methods: We collected RSV samples and isolates from Mexico, Argentina, Belgium, Italy, Germany, Australia, South Africa, and the USA from the years 1998-2010. Both Sanger and next-generation sequencing with the Illumina and 454 platforms were used to sequence the whole genomes of RSV A and B. Phylogenetic analyses were performed using the Bayesian and maximum likelihood methods of phylogenetic inference.

Results: We sequenced the genomes of 34 RSVA and 23 RSVB viruses. Phylogenetic analysis showed that the RSVA genome evolves at an estimated rate of 6.72 × 10(-4) substitutions/site/year (95% HPD 5.61 × 10(-4) to 7.6 × 10(-4)) and for RSVB the evolutionary rate was 7.69 × 10(-4) substitutions/site/year (95% HPD 6.81 × 10(-4) to 8.62 × 10(-4)). We found multiple clades co-circulating globally for both RSV A and B. The predominant clades were GA2 and GA5 for RSVA and BA for RSVB.

Conclusions: Our analyses showed that RSV circulates on a global scale with the same predominant clades of viruses being found in countries around the world. However, the distribution of clades can change rapidly as new strains emerge. We did not observe a strong spatial structure in our trees, with the same three main clades of RSV co-circulating globally, suggesting that the evolution of RSV is not strongly regionalized.

No MeSH data available.


Related in: MedlinePlus