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Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized1-7, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.
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Owing to the frequency and severity of human seasonal influenza A/H3N2 virus epidemics, recent work has focused on the global circulation dynamics of H3N2 viruses1-7. Studies have shown that, each year, H3N2 epidemics worldwide result from the introduction of new genetic variants from East and Southeast (E-SE) Asia, where viruses circulate via a network of temporally overlapping epidemics1,2,4,5, rather than local persistence1,3,6,7. In addition to H3N2, H1N1 viruses and two antigenically diverged lineages of influenza B viruses, B/Victoria/2/1987-like (Vic) and B/Yamagata/16/1988-like (Yam), circulate among humans with lower but substantial disease burdens8,9. Despite their importance, the global circulation dynamics of former seasonal H1N1 viruses (preceding the 2009 pandemic) and B viruses have been largely neglected.
Given that influenza A and B viruses cause similar symptoms and evolve by similar mechanisms of immune escape, we hypothesized that each would follow similar patterns of global circulation, with new genetic variants originating in East and Southeast Asia that rapidly replace existing genetic variants. To test...