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The contrasting phylodynamics of human influenza B viruses.

Vijaykrishna D, Holmes EC, Joseph U, Fourment M, Su YC, Halpin R, Lee RT, Deng YM, Gunalan V, Lin X, Stockwell TB, Fedorova NB, Zhou B, Spirason N, Kühnert D, Bošková V, Stadler T, Costa AM, Dwyer DE, Huang QS, Jennings LC, Rawlinson W, Sullivan SG, Hurt AC, Maurer-Stroh S, Wentworth DE, Smith GJ, Barr IG - Elife (2015)

Bottom Line: Although considerable attention has been paid to influenza A viruses, a lack of equivalent data means that an integrated evolutionary and epidemiological framework has until now not been available for influenza B viruses, despite their significant disease burden.Through the analysis of over 900 full genomes from an epidemiological collection of more than 26,000 strains from Australia and New Zealand, we reveal fundamental differences in the phylodynamics of the two co-circulating lineages of influenza B virus (Victoria and Yamagata), showing that their individual dynamics are determined by a complex relationship between virus transmission, age of infection, and receptor binding preference.In sum, this work identifies new factors that are important determinants of influenza B evolution and epidemiology.

View Article: PubMed Central - PubMed

Affiliation: Duke-NUS Graduate Medical School, Singapore, Singapore.

ABSTRACT
A complex interplay of viral, host, and ecological factors shapes the spatio-temporal incidence and evolution of human influenza viruses. Although considerable attention has been paid to influenza A viruses, a lack of equivalent data means that an integrated evolutionary and epidemiological framework has until now not been available for influenza B viruses, despite their significant disease burden. Through the analysis of over 900 full genomes from an epidemiological collection of more than 26,000 strains from Australia and New Zealand, we reveal fundamental differences in the phylodynamics of the two co-circulating lineages of influenza B virus (Victoria and Yamagata), showing that their individual dynamics are determined by a complex relationship between virus transmission, age of infection, and receptor binding preference. In sum, this work identifies new factors that are important determinants of influenza B evolution and epidemiology.

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Related in: MedlinePlus

Structural view of mutational drift in influenza A and Bviruses.Amino acid mutations accumulated over 10 years (red) using differentrotations of the hemagglutinin monomer structure of influenza B Victoria(2002–2012) (PDB:4FQM) (A), Yamagata(2002–2012) (PDB:4FQM) (B) in comparison to seasonalinfluenza A H3N2 (1999–2009) (PDB:2YP4) (C), and H1N1(1997–2007) (PDB:3UBE) (D) viruses. Arrows point toreceptor binding pocket.DOI:http://dx.doi.org/10.7554/eLife.05055.019
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fig11s1: Structural view of mutational drift in influenza A and Bviruses.Amino acid mutations accumulated over 10 years (red) using differentrotations of the hemagglutinin monomer structure of influenza B Victoria(2002–2012) (PDB:4FQM) (A), Yamagata(2002–2012) (PDB:4FQM) (B) in comparison to seasonalinfluenza A H3N2 (1999–2009) (PDB:2YP4) (C), and H1N1(1997–2007) (PDB:3UBE) (D) viruses. Arrows point toreceptor binding pocket.DOI:http://dx.doi.org/10.7554/eLife.05055.019

Mentions: Finally, we sought to determine whether differences in the evolutionary andepidemiological dynamics between the two influenza B lineages resulted from variationin HA structure and binding preferences. First, we compared amino acid substitutionsper site within and between influenza virus lineages from 2002 to 2012 and mappedthese onto structural models of representative influenza B virus strains (Figure 11). The higher rates of amino acidchange observed in the Victoria HA (Figure11A) were consistent with the stronger selective pressures on this virallineage. Importantly, these changes occurred in three major clusters situated around21, 29, and 37 Å to the RBP of the HA domain that also comprises potentialantigenic sites. Notably, all changes in the closest cluster (21 Å) werecomprised exclusively of Victoria lineage amino acid changes, while the few changesobserved in Yamagata lineage viruses were distant to the RBP (Figure 11C). Overall, however, amino acid changes in bothinfluenza B virus lineages were less frequent than those in influenza A virusessampled over a similar time period, with the H3N2 viruses showing more extensivestructural change (Figure 11—figuresupplement 1).10.7554/eLife.05055.018Figure 11.Structural view of the HA showing mutational accumulation and lineagedifferences.


The contrasting phylodynamics of human influenza B viruses.

Vijaykrishna D, Holmes EC, Joseph U, Fourment M, Su YC, Halpin R, Lee RT, Deng YM, Gunalan V, Lin X, Stockwell TB, Fedorova NB, Zhou B, Spirason N, Kühnert D, Bošková V, Stadler T, Costa AM, Dwyer DE, Huang QS, Jennings LC, Rawlinson W, Sullivan SG, Hurt AC, Maurer-Stroh S, Wentworth DE, Smith GJ, Barr IG - Elife (2015)

Structural view of mutational drift in influenza A and Bviruses.Amino acid mutations accumulated over 10 years (red) using differentrotations of the hemagglutinin monomer structure of influenza B Victoria(2002–2012) (PDB:4FQM) (A), Yamagata(2002–2012) (PDB:4FQM) (B) in comparison to seasonalinfluenza A H3N2 (1999–2009) (PDB:2YP4) (C), and H1N1(1997–2007) (PDB:3UBE) (D) viruses. Arrows point toreceptor binding pocket.DOI:http://dx.doi.org/10.7554/eLife.05055.019
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383373&req=5

fig11s1: Structural view of mutational drift in influenza A and Bviruses.Amino acid mutations accumulated over 10 years (red) using differentrotations of the hemagglutinin monomer structure of influenza B Victoria(2002–2012) (PDB:4FQM) (A), Yamagata(2002–2012) (PDB:4FQM) (B) in comparison to seasonalinfluenza A H3N2 (1999–2009) (PDB:2YP4) (C), and H1N1(1997–2007) (PDB:3UBE) (D) viruses. Arrows point toreceptor binding pocket.DOI:http://dx.doi.org/10.7554/eLife.05055.019
Mentions: Finally, we sought to determine whether differences in the evolutionary andepidemiological dynamics between the two influenza B lineages resulted from variationin HA structure and binding preferences. First, we compared amino acid substitutionsper site within and between influenza virus lineages from 2002 to 2012 and mappedthese onto structural models of representative influenza B virus strains (Figure 11). The higher rates of amino acidchange observed in the Victoria HA (Figure11A) were consistent with the stronger selective pressures on this virallineage. Importantly, these changes occurred in three major clusters situated around21, 29, and 37 Å to the RBP of the HA domain that also comprises potentialantigenic sites. Notably, all changes in the closest cluster (21 Å) werecomprised exclusively of Victoria lineage amino acid changes, while the few changesobserved in Yamagata lineage viruses were distant to the RBP (Figure 11C). Overall, however, amino acid changes in bothinfluenza B virus lineages were less frequent than those in influenza A virusessampled over a similar time period, with the H3N2 viruses showing more extensivestructural change (Figure 11—figuresupplement 1).10.7554/eLife.05055.018Figure 11.Structural view of the HA showing mutational accumulation and lineagedifferences.

Bottom Line: Although considerable attention has been paid to influenza A viruses, a lack of equivalent data means that an integrated evolutionary and epidemiological framework has until now not been available for influenza B viruses, despite their significant disease burden.Through the analysis of over 900 full genomes from an epidemiological collection of more than 26,000 strains from Australia and New Zealand, we reveal fundamental differences in the phylodynamics of the two co-circulating lineages of influenza B virus (Victoria and Yamagata), showing that their individual dynamics are determined by a complex relationship between virus transmission, age of infection, and receptor binding preference.In sum, this work identifies new factors that are important determinants of influenza B evolution and epidemiology.

View Article: PubMed Central - PubMed

Affiliation: Duke-NUS Graduate Medical School, Singapore, Singapore.

ABSTRACT
A complex interplay of viral, host, and ecological factors shapes the spatio-temporal incidence and evolution of human influenza viruses. Although considerable attention has been paid to influenza A viruses, a lack of equivalent data means that an integrated evolutionary and epidemiological framework has until now not been available for influenza B viruses, despite their significant disease burden. Through the analysis of over 900 full genomes from an epidemiological collection of more than 26,000 strains from Australia and New Zealand, we reveal fundamental differences in the phylodynamics of the two co-circulating lineages of influenza B virus (Victoria and Yamagata), showing that their individual dynamics are determined by a complex relationship between virus transmission, age of infection, and receptor binding preference. In sum, this work identifies new factors that are important determinants of influenza B evolution and epidemiology.

Show MeSH
Related in: MedlinePlus