Abstract

The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016–17 raises concerns about the epizootic potential of these viruses. We investigated the evolution and adaptation of H7N9 viruses by analyzing available data and newly generated virus sequences isolated in Guangdong Province, China, during 2015–2017. Phylogenetic analyses showed that circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Hemagglutination inhibition assays performed on serum samples from patients infected with these viruses identified 3 antigenic clusters for 16 strains of different virus lineages. We used ancestral sequence reconstruction to identify parallel amino acid changes on multiple separate lineages. We inferred that mutations in hemagglutinin occur primarily at sites involved in receptor recognition or antigenicity. Our results indicate that highly pathogenic strains likely emerged from viruses circulating in eastern Guangdong Province during March 2016 and are associated with a high rate of adaptive molecular evolution.

Highlights

  • The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016–17 raises concerns about the epizootic potential of these viruses

  • H7N9 virus has evolved in a clock-like manner (Figure 1)

  • Different H7N9 virus lineages are associated with different epidemiologic patterns (Figures 2, 3)

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Summary

Introduction

The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016–17 raises concerns about the epizootic potential of these viruses. Preliminary epidemiologic data suggested that most human infections in the current fifth epidemic wave were caused by viruses from the Yangtze River Delta region [5] (previously named lineage C viruses) [3] These viruses, in contrast to viruses from the Pearl River Delta region (previously named lineage B viruses) [3], appear to exhibit reduced cross-reactivity with existing candidate vaccine virus strains [9]. Information necessary to clarify this situation includes geographic distribution of currently circulating H7N9 virus lineages, origin and genetic composition of newly emerged HP H7N9 viruses, and evolutionary and structural characterization of mutations associated with the fifth epidemic wave of these viruses. We conducted structural and evolutionary analyses of these strains and characterized the evolution and emergence of currently circulating H7N9 viruses in China

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