Exploring the Molecular Epidemiology and Evolutionary Dynamics of Influenza A Virus in Taiwan

Jih-Hui Lin,Ju-Chien Cheng,Yung-Cheng Lin,Shu-Chun Chiu,Marco Salemi,Hsin-Fu Liu,Ho-Sheng Wu,Yury E Khudyakov

doi:10.1371/journal.pone.0061957

Abstract

The evolution and population dynamics of human influenza in Taiwan is a microcosm of the viruses circulating worldwide, which has not yet been studied in detail. We collected 343 representative full genome sequences of human influenza A viruses isolated in Taiwan between 1979 and 2009. Phylogenetic and antigenic data analysis revealed that H1N1 and H3N2 viruses consistently co-circulated in Taiwan, although they were characterized by different temporal dynamics and degrees of genetic diversity. Moreover, influenza A viruses of both subtypes underwent internal gene reassortment involving all eight segments of the viral genome, some of which also occurred during non-epidemic periods. The patterns of gene reassortment were different in the two subtypes. The internal genes of H1N1 viruses moved as a unit, separately from the co-evolving HA and NA genes. On the other hand, the HA and NA genes of H3N2 viruses tended to segregate consistently with different sets of internal gene segments. In particular, as reassortment occurred, H3HA always segregated as a group with the PB1, PA and M genes, while N2NA consistently segregated with PB2 and NP. Finally, the analysis showed that new phylogenetic lineages and antigenic variants emerging in summer were likely to be the progenitors of the epidemic strains in the following season. The synchronized seasonal patterns and high genetic diversity of influenza A viruses observed in Taiwan make possible to capture the evolutionary dynamic and epidemiological rules governing antigenic drift and reassortment and may serve as a “warning” system that recapitulates the global epidemic.

Highlights

Influenza A virus is one of the most active pathogens in Taiwan causing regular, yearly epidemics worldwide associated with significant morbidity and mortality in humans [1,2]
Five of the past ten influenza seasons in Taiwan were dominated by H1N1, which were preceded by H3N2 during the most recent 5 years (Figure S1)
The current study represents the first in depth phylodynamic and epidemiologic data analysis of human influenza A viruses in the region, based on a large full genome data set, which included H3N2 and H1N1 strains collected over 30 years

Summary

Introduction

Influenza A virus is one of the most active pathogens in Taiwan causing regular, yearly epidemics worldwide associated with significant morbidity and mortality in humans [1,2]. H1N1 and H3N2 are currently the major circulating subtypes and have been infecting the human population for several decades. The underlying basis for the annual recurrence of seasonal influenza still defies simple explanations [3,4]. It was previously believed that influenza pandemics occurred at 10- to 14-year intervals, but this has not been the case for H3N2 outbreaks over the past 40 years, since the emergence of the 1968 pandemic strain [3]. It was believed that cocirculation of different influenza A subtypes within a season was not likely. Recent studies have shown that H1N1 and H3N2 viruses have been circulating together since 1977 [5,6]

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