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    Discussion - Global circulation patterns of seasonal influenza viruses vary with antigenic drift

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    We have recently done a lot of study on global circulation dynamics of H3N2 viruses (seasonal influenza A).

    • new variants introduced from E-SE Asia
    • circulate via temporally overlapping epidemics
      • not local persistence
    We have not, however, done much significant work on studying the global circulation dynamics of H1N1 viruses (seasonal influenza B).
    • similar symptoms and methods of immune escape to influenza B, but lower disease burdens
      • hypothesis: global circulation dynamics would be similar for both strains of influenza - new variants originating from E-SE Asia, new genotypes rapidly displace old (is this the null hypothesis, that there is no difference?)
    • compare global circulation patterns of the haemagglutinin (HA) genes of H3N2 and H1N1 viruses
      • get data from WHO Global Influenza Research Database
      • reduce bias - subsample to equitable spatiotemporal distributions
      • estimate temporally resolved phylogenetic trees for each subsample
        • results: faster rates of nucleotide/amino acid mutation in H3N2, more genealogical diversity in H1N1
          • explained by antigenic drift correlating with mutation rate, driving adaptive evolution, depleting HA genetic diversity
          • H3N2 coalesces to the "trunk" of the tree within a couple of years, trunk viruses originating in E-SE Asia and India (a more recent contributor on a global scale)
        • global circulation patterns differed between H3N2 and H1N1 - hypothesis disproved
          • geographic segregation
          • patterns of persistence
    • explore differences further
      • use spatiotemporally resolved phylogenies to estimate virus movement rates and amounts between regions
      • hypothesis: there is a relationship between rates of global movement and rates of antigenic drift, and lower rates of immune escape in H1N1 would result in younger average ages of infection (infect more children)
        • differences in age classes affected may explain differences in global circulation - children to not travel as far or as often as adults
      • multi-patch transmission model
        • age-independent mixing between patches scenario and age-stratified mixing scenario
        • age-independent results: faster antigenic drift, resulting in greater incidence and more adult infections, and faster spread of new strains
        • age-stratified results: intensified effects of antigenic drift on migration rate, movement differed between patches consistent with data for H3N2 and H1N1 viruses
        • varying transmission rate instead of antigenic mutation rate yields the same results
        • hypothesis supported

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