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.
To develop new therapies against infections caused by a virus, it is important to
understand the virus's history—where, when, and why it has caused
disease and how it has changed over time. For example, new human strains of the
influenza type A virus originate from strains that infect animals and rapidly can
become common in human populations. In contrast, influenza type B virus strains
almost exclusively infect humans and are continuously present in human populations.
Both types have a detrimental impact on global health, but the type B viruses are
less well understood, partly because outbreaks have not been as extensively
Vijaykrishna et al. have now investigated the history of the two strains of the
influenza type B virus—called Victoria and Yamagata—that currently
circulate in humans. To do this, they inspected the genetic sequences of 908 viruses
taken from samples of confirmed type B infections collected across Australia and New
Zealand over 13 years.
Individual virus particles of the same strain have genetic sequences that are very
similar, but not completely identical. Vijaykrishna et al. showed that the diversity
of the genetic sequences from the Victoria strain fluctuated between seasons, and
particular genetic variants of Victoria only persisted in the population for
1–3 years. This indicates that Victoria viruses are under a lot of pressure to
evolve, which results in so-called ‘bottlenecks’ whereby only the
viruses carrying particular varieties of genetic sequence survive. This fluctuating
pattern resembles that of the better-understood type A seasonal flu strain H3N2.
On the other hand, there was little change in the genetic diversity of the Yamagata
strains sampled over the same 13-year period. The Yamagata viruses have diversified
to a greater extent and several different ‘varieties’ of the virus tend
to circulate together for long periods of time. For example, the three varieties of
Yamagata virus circulating in 2013 evolved from a common parent virus that was
circulating around 10 years ago.
Vijaykrishna et al. found that between disease outbreaks, there was greater variation
in the ability of Victoria viruses to be transmitted in humans, but that they were
generally more easily transmitted than the Yamagata viruses. Victoria viruses tend to
infect younger patients than Yamagata viruses, which is thought to be due to
differences in the molecules that help the viruses enter the cells of the respiratory
These findings suggests that it might be possible to eradicate the more slowly
evolving influenza B Yamagata virus through mass vaccination programs using existing
vaccines. This would then allow researchers to focus on developing effective vaccines
to target the other strains of influenza virus.