Abstract

Subtype H7 avian–origin influenza A viruses (AIVs) have caused at least 500 confirmed human infections since 2003 and culling of >75 million birds in recent years. Here we antigenically and genetically characterized 93 AIV isolates from North America (85 from migratory waterfowl [1976–2010], 7 from domestic poultry [1971–2012], and 1 from a seal [1980]). The hemagglutinin gene of these H7 viruses are separated from those from Eurasia. Gradual accumulation of nucleotide and amino acid substitutions was observed in the hemagglutinin of H7 AIVs from waterfowl and domestic poultry. Genotype characterization suggested that H7 AIVs in wild birds form diverse and transient internal gene constellations. Serologic analyses showed that the 93 isolates cross-reacted with each other to different extents. Antigenic cartography showed that the average antigenic distance among them was 1.14 units (standard deviation [SD], 0.57 unit) and that antigenic diversity among the H7 isolates we tested was limited. Our results suggest that the continuous genetic evolution has not led to significant antigenic diversity for H7 AIVs from North America. These findings add to our understanding of the natural history of IAVs and will inform public health decision-making regarding the threat these viruses pose to humans and poultry.

Highlights

  • IAVs evolve by 2 major mechanisms: mutation and reassortment

  • In Italy, vaccine was used against H7N1 virus in 2000 and against H7N3 virus in 2002; vaccines have been used in Pakistan since 1995 to control H7N3 virus; and in North America, vaccine was used against a 2003 H7N2 virus outbreak in Connecticut, United States, and against the on-going H7N3 virus outbreak in Mexico

  • Phylogenetic analyses showed that HA gene of H7 avian influenza viruses (AIVs) was divided into 2 geographically dependent lineages: Eurasian and North American (Fig. S1)

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Summary

Introduction

IAVs evolve by 2 major mechanisms: mutation and reassortment. Point mutations within surface glycoproteins HA and NA can lead to a small antigenic change, so called antigenic drift. Reassortment occurs frequently between IAVs2–6, and it facilitates generation of epidemic and pandemic influenza strains[7,8] Both antigenic drift and antigenic shift allow IAVs to evade the herd immunity established from previous influenza infections or vaccination. Migratory waterfowl introduced highly pathogenic avian influenza (HPAI) A subtype H5 viruses from Eurasia to North America, resulting in more than 200 cases among domestic poultry in the northwestern and mid-western United States and the culling of more than 40 million birds[10,11]. Understanding the antigenic diversity of H7 AIVs circulating in North America will facilitate our understanding of the natural history of IAVs and the detection of influenza virus antigenic variants and development of effective strategies for disease prevention and control. The genomic sequences were analyzed to determine the genetic evolution dynamics of H7 AIVs in North America

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