Explaining the geographic origins of seasonal influenza A (H3N2)

TL;DR

This study uses simulations to explore how ecological and evolutionary factors, especially the basic reproductive number ($R_0$), influence the geographic origins and spread of antigenically novel influenza A (H3N2) strains, challenging the emphasis on seasonality and air traffic.

Contribution

It demonstrates that a region's $R_0$ significantly impacts influenza evolution and spread, providing a new perspective beyond traditional explanations like seasonality and air traffic.

Findings

Higher $R_0$ in a region increases its likelihood of exporting successful strains.

Seasonality alone does not predict antigenic advancement of strains.

Regional demographic factors have minor effects on influenza phylogeography.

Abstract

Most antigenically novel and evolutionarily successful strains of seasonal influenza A (H3N2) originate in East, South, and Southeast Asia. To understand this pattern, we simulated the ecological and evolutionary dynamics of influenza in a host metapopulation representing the temperate north, tropics, and temperate south. Although seasonality and air traffic are frequently used to explain global migratory patterns of influenza, we find that other factors may have a comparable or greater impact. Notably, a region's basic reproductive number ($R_0$) strongly affects the antigenic evolution of its viral population and the probability that its strains will spread and fix globally: a 17-28% higher $R_0$ in one region can explain the observed patterns. Seasonality, in contrast, increases the probability that a tropical (less seasonal) population will export evolutionarily successful strains but alone does not predict that these strains will be antigenically advanced. The relative sizes of different host populations, their birth and death rates, and the region in which H3N2 first appears affect influenza's phylogeography in different but relatively minor ways. These results suggest general principles that dictate the spatial dynamics of antigenically evolving pathogens and offer predictions for how changes in human ecology might affect influenza evolution.