Abstract
Understanding the spatio-temporal 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, based on analyses of 9,604 hemagglutinin sequences of human seasonal influenza viruses from 2000–2012, 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. While genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast (E-SE) Asia, genetic variants of A/H1N1 and B viruses persisted across multiple seasons and exhibited complex global dynamics with E-SE 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 likely drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology and human behavior.
Highlights
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 viruses[1,2,3,4,5,6,7]
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 epidemics[1,2,4,5], rather than local persistence[1,3,6,7]
By inferring geographic ancestry using Bayesian phylogeographic methods[15], we found a consistent pattern for H3N2 viruses (Fig. 1a) in which viruses worldwide rapidly coalesce to the trunk of the tree, with trunk viruses mostly originating from E-SE Asia (Extended Data Fig. 2a)
Summary
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 viruses[1,2,3,4,5,6,7]. These long circulating E-SE Asian lineages were most apparent for Vic viruses where two lineages (Fig. 1c, nodes 1 and 2) persisted independently in China and SE Asia for over 5 years without spreading to other regions and led to the co-circulation of three distinct Vic antigenic variants in different parts of the world during 2007/2008 (Extended Data Fig. 5a).
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