Phylogenetic analysis reveals the global migration of seasonal influenza A viruses

Abstract

The winter seasonality of influenza A virus in temperate climates is one of the most widely recognized, yet least understood, epidemiological patterns in infectious disease. Central to understanding what drives the seasonal emergence of this important human pathogen is determining what becomes of the virus during the non-epidemic summer months. Herein, we take a step towards elucidating the seasonal emergence of influenza virus by determining the evolutionary relationship between populations of influenza A virus sampled from opposite hemispheres. We conducted a phylogenetic analysis of 487 complete genomes of human influenza A/H3N2 viruses collected between 1999 and 2005 from Australia and New Zealand in the southern hemisphere, and a representative sub-sample of viral genome sequences from 413 isolates collected in New York state, United States, representing the northern hemisphere. We show that even in areas as relatively geographically isolated as New Zealand's South Island and Western Australia, global viral migration contributes significantly to the seasonal emergence of influenza A epidemics, and that this migration has no clear directional pattern. These observations run counter to suggestions that local epidemics are triggered by the climate-driven reactivation of influenza viruses that remain latent within hosts between seasons or transmit at low efficiency between seasons. However, a complete understanding of the seasonal movements of influenza A virus will require greatly expanded global surveillance, particularly of tropical regions where the virus circulates year-round, and during non-epidemic periods in temperate climate areas.

Figure 1. Models for the Global Evolution of Influenza Virus

Two phylogenetic hypotheses depicting the evolution of A/H3N2 influenza virus by (A) global migration, in which isolates from adjacent seasons in the northern and southern hemispheres are interspersed topologically, or by (B) reactivation of latent virus, in which isolates from the northern hemisphere give rise, in situ, to isolates that circulate in the same locality the next season, and thus are topologically linked (likewise for southern hemisphere viruses).

Figure 2. Phylogenetic Relationships of the NA Gene of A/H3N2 Influenza Viruses Sampled from New York State (n = 52), New Zealand (n = 51), Australia (n = 45), and Globally (n = 22) from 1998 to 2005, Estimated Using ML

Viral isolates from New York state are highlighted in orange, isolates from New Zealand in green, isolates from Australia in blue, and global isolates in pink. Light yellow rectangles identify viral clades, with numbers in white boxes giving bootstrap values for key nodes (>70%). To clarify reassortment events, capital letters in blue refer to clades that appear in section I of the tree (denoted in pink) on the phylogeny of the concatenated six non-surface glycoproteins; lowercase letters in red refer to clades contained within section II (denoted in light green); and lowercase roman numerals in dark green refer to clades outside sections I and II. Bootstrap values highlighted in yellow identify nodes that define a cross-hemisphere migration event. The tree is rooted by isolate A/New York/327/1999 from the 1998–1999 season (i.e., the earliest sampled isolate), and all horizontal branch lengths are drawn to a scale of nucleotide substitutions per site.

Figure 3. Phylogenetic Relationships of the HA Gene of A/H3N2 Influenza Viruses Sampled from New York State (n = 52), New Zealand (n = 51), Australia (n = 45), and Globally (n = 13) from 1998 to 2005, Estimated Using ML

Color scheme, rooting, scale, and symbols are the same as those used in Figure 2.

Figure 4. Phylogenetic Relationships of the Concatenated Six Non-Surface Glycoprotein Segments of A/H3N2 Influenza Viruses Sampled from New York State (n = 52), New Zealand (n = 51), and Australia (n = 45) from 1998 to 2005, Estimated Using ML

Color scheme, rooting, scale, and symbols are the same as those used in Figure 2.