Abstract

Three H14 influenza A virus (IAV) isolates recovered in 2010 during routine virus surveillance along the Mississippi Migratory Bird Flyway in Wisconsin, U.S.A. raised questions about the natural history of these rare viruses. These were the first H14 IAV isolates recovered in the Western Hemisphere and the only H14 IAV isolates recovered since the original four isolates in 1982 in Asia. Full length genomic sequencing of the 2010 H14 isolates demonstrated the hemagglutinin (HA) gene from the 1982 and 2010 H14 isolates showed 89.6% nucleotide and 95.6% amino acid similarity and phylogenetic analysis of these viruses placed them with strong support within the H14 subtype lineage. The level of genomic divergence observed between the 1982 and 2010 viruses provides evidence that the H14 HA segment was circulating undetected in hosts and was not maintained in environmental stasis. Further, the evolutionary relationship observed between 1982 H14 and the closely related H4 subtype HA segments were similar to contemporary comparisons suggesting limited adaptive divergence between these sister subtypes. The nonstructural (NS) segment of one 2010 isolate was placed in a NS clade isolated infrequently over the last several decades that includes the NS segment from a previously reported 1982 H14 isolate indicating the existence of an unidentified pool of genomic diversity. An additional neuraminidase reassortment event indicated a recent inter-hemispheric gene flow from Asia into the center of North America. These results demonstrate temporal and spatial gaps in the understanding of IAV natural history. Additionally, the reassortment history of these viruses raises concern for the inter-continental spread of IAVs and the efficacy of current IAV surveillance efforts in detecting genomic diversity of viruses circulating in wild birds.

Highlights

  • All novel influenza A virus (IAV) strains resulting in global pandemics since the 20th century have contained genetic elements from avian-origin IAV lineages [1,2]

  • Understanding the ecology of IAVs is complicated by the ability of migratory birds to transport IAVs over large geographic expanses facilitating the movement of viruses and their genomic segments worldwide [11]

  • Problematic, IAVs may persist in environmental stasis for long periods of time, undetected by surveillance focused on wild birds, until a time when agent, host, or environmental factors allow for reemergence in susceptible hosts within a region [14]

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Summary

Introduction

All novel influenza A virus (IAV) strains resulting in global pandemics since the 20th century have contained genetic elements from avian-origin IAV lineages [1,2]. It is well established that wild birds in the order Anseriformes and Chardriiformes are natural reservoirs for antigenically and genetically diverse populations of influenza A viruses, including 16 of the 17 known influenza A virus hemagglutinin (HA) subtypes and 9 of the 10 known neuraminidase (NA) subtypes [3,4,5,6,7]. Many of these subtypes have strong host species preferences or even appear to be host species specific [7,8]. The rapid spread and lack of detection of many IAVs is concerning when one considers the highly pathogenic strains of IAV which are lethal to domestic poultry and humans

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