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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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Estimates of Re withvarious S0 values.Estimates of effective population size,Re, using variousS0 values for all Victoria(A) and Yamagata (C) lineage viruses isolatedin Australia and for the largest monophyletic group of Victoria(B) viruses in Australia that clearly represent a singleintroduction.DOI:http://dx.doi.org/10.7554/eLife.05055.009
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fig5s1: Estimates of Re withvarious S0 values.Estimates of effective population size,Re, using variousS0 values for all Victoria(A) and Yamagata (C) lineage viruses isolatedin Australia and for the largest monophyletic group of Victoria(B) viruses in Australia that clearly represent a singleintroduction.DOI:http://dx.doi.org/10.7554/eLife.05055.009

Mentions: The BDSIR model assumes a closed epidemic, but the large-scale phylogenies generatedusing all available global data indicated that each of the annual epidemics werecaused by the introduction of multiple viral lineages that went extinct locally bythe end of the seasonal epidemic (data not shown). We therefore investigated theeffect of virus migration on the estimates ofRe. First, we identified lineagesthat conformed to the assumption of a closed epidemic (i.e., lineages resulting froma single introduction into Australia and New Zealand) and with a sufficiently largelocal transmission for analysis (i.e., Victoria lineage viruses in 2005, 2006 and2008). An independent estimation of Refor each of these lineages produced a minor but non-significant variation to thoseobserved for the entire epidemic (Figure5—figure supplement 1B), indicating that, on average, theRe estimates for lineages resultingfrom multiple introductions were similar. Next, we used a continuous-time Markovchain (CTMC) phylogeographic process (Minin andSuchard, 2008) to estimate the number of migration events into and fromAustralia and New Zealand during the same period (Figure 6). This indicated that the number of introductions per year wasgreater for the Yamagata lineage (15–22, mean state transition count in allyears) than for Victoria (3–8, except 16 and 14 during 2010 and 2011,respectively) (Figure 6), further suggestingan inverse relationship between Re(Figure 5) and the number of introductionevents. Indeed, our results show that introductions of viruses with greatertransmission efficiency (i.e., high Re),such as Victoria/2008, resulted in the epidemic dominance of such single strains,whereas epidemics of the Yamagata lineage with lowerRe values likely resulted inslower and shorter transmission chains with reduced competition, in turn allowing theco-circulation (and detection) of multiple introduced lineages. Additionally, weidentified that, combined, Australia and New Zealand were net importers of influenzaviruses, except during 2002 and 2008 when the net export of the Victoria lineage wassimilar to the import observed during the same years (Figure 6). The higher transmission rate for Victoria/2008 viruses (i.e.,B/Brisbane/60/2008-like viruses) may have also caused the successful seeding of theseviruses globally (as described above). Taken together, our results support theconcept of a global metapopulation seeding subsequent epidemics elsewhere (Bedford et al., 2010; Bahl et al., 2011), provided the virus is transmittedefficiently as observed during 2008 in this study.10.7554/eLife.05055.010Figure 6.Estimation of migration of influenza B viruses into and out of Australiaand New Zealand.


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)

Estimates of Re withvarious S0 values.Estimates of effective population size,Re, using variousS0 values for all Victoria(A) and Yamagata (C) lineage viruses isolatedin Australia and for the largest monophyletic group of Victoria(B) viruses in Australia that clearly represent a singleintroduction.DOI:http://dx.doi.org/10.7554/eLife.05055.009
© Copyright Policy
Related In: Results  -  Collection

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

fig5s1: Estimates of Re withvarious S0 values.Estimates of effective population size,Re, using variousS0 values for all Victoria(A) and Yamagata (C) lineage viruses isolatedin Australia and for the largest monophyletic group of Victoria(B) viruses in Australia that clearly represent a singleintroduction.DOI:http://dx.doi.org/10.7554/eLife.05055.009
Mentions: The BDSIR model assumes a closed epidemic, but the large-scale phylogenies generatedusing all available global data indicated that each of the annual epidemics werecaused by the introduction of multiple viral lineages that went extinct locally bythe end of the seasonal epidemic (data not shown). We therefore investigated theeffect of virus migration on the estimates ofRe. First, we identified lineagesthat conformed to the assumption of a closed epidemic (i.e., lineages resulting froma single introduction into Australia and New Zealand) and with a sufficiently largelocal transmission for analysis (i.e., Victoria lineage viruses in 2005, 2006 and2008). An independent estimation of Refor each of these lineages produced a minor but non-significant variation to thoseobserved for the entire epidemic (Figure5—figure supplement 1B), indicating that, on average, theRe estimates for lineages resultingfrom multiple introductions were similar. Next, we used a continuous-time Markovchain (CTMC) phylogeographic process (Minin andSuchard, 2008) to estimate the number of migration events into and fromAustralia and New Zealand during the same period (Figure 6). This indicated that the number of introductions per year wasgreater for the Yamagata lineage (15–22, mean state transition count in allyears) than for Victoria (3–8, except 16 and 14 during 2010 and 2011,respectively) (Figure 6), further suggestingan inverse relationship between Re(Figure 5) and the number of introductionevents. Indeed, our results show that introductions of viruses with greatertransmission efficiency (i.e., high Re),such as Victoria/2008, resulted in the epidemic dominance of such single strains,whereas epidemics of the Yamagata lineage with lowerRe values likely resulted inslower and shorter transmission chains with reduced competition, in turn allowing theco-circulation (and detection) of multiple introduced lineages. Additionally, weidentified that, combined, Australia and New Zealand were net importers of influenzaviruses, except during 2002 and 2008 when the net export of the Victoria lineage wassimilar to the import observed during the same years (Figure 6). The higher transmission rate for Victoria/2008 viruses (i.e.,B/Brisbane/60/2008-like viruses) may have also caused the successful seeding of theseviruses globally (as described above). Taken together, our results support theconcept of a global metapopulation seeding subsequent epidemics elsewhere (Bedford et al., 2010; Bahl et al., 2011), provided the virus is transmittedefficiently as observed during 2008 in this study.10.7554/eLife.05055.010Figure 6.Estimation of migration of influenza B viruses into and out of Australiaand New Zealand.

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