Abstract

Reassortment among co-infecting influenza A viruses (IAVs) is an important source of viral diversity and can facilitate expansion into novel host species. Indeed, reassortment played a key role in the evolution of the last three pandemic IAVs. Observed patterns of reassortment within a coinfected host are likely to be shaped by several factors, including viral load, the extent of viral mixing within the host and the stringency of selection. These factors in turn are expected to vary among the diverse host species that IAV infects. To investigate host differences in IAV reassortment, here we examined reassortment of two distinct avian IAVs within their natural host (mallards) and a mammalian model system (guinea pigs). Animals were co-inoculated with A/wildbird/California/187718-36/2008 (H3N8) and A/mallard/Colorado/P66F1-5/2008 (H4N6) viruses. Longitudinal samples were collected from the cloaca of mallards or the nasal tract of guinea pigs and viral genetic exchange was monitored by genotyping clonal isolates from these samples. Relative to those in guinea pigs, viral populations in mallards showed higher frequencies of reassortant genotypes and were characterized by higher genotype richness and diversity. In line with these observations, analysis of pairwise segment combinations revealed lower linkage disequilibrium in mallards as compared to guinea pigs. No clear longitudinal patterns in richness, diversity or linkage disequilibrium were present in either host. Our results reveal mallards to be a highly permissive host for IAV reassortment and suggest that reduced viral mixing limits avian IAV reassortment in a mammalian host.

Highlights

  • Influenza A viruses (IAVs) infect a broad range of host species

  • Reassortment rates were lower, fewer unique genotypes were detected and relatively high prevalence of parental genotypes resulted in low diversity. These findings indicate that mallards are highly permissive for avian IAV reassortment, whereas mammalian hosts may present a less permissive environment

  • Through experimental coinfection of mallards and guinea pigs with distinct IAVs typical of those that circulate widely in North American ducks, we examined the efficiency of IAV genetic exchange in both a natural host and a model mammalian host

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Summary

Introduction

Influenza A viruses (IAVs) infect a broad range of host species. Many diverse lineages circulate in waterfowl (Anseriformes) and shorebirds (Charadriformes), with 16 hemagglutinin and 9 neuraminidase subtypes represented. This diverse viral gene pool is the ancestral source of IAV lineages circulating in poultry, swine, humans, and other mammalian hosts [1,2]. Host barriers to infection limit the range of hosts within which a given IAV lineage circulates, spillovers occur occasionally and can seed novel lineages [3,4]. The segmented nature of the IAV genome allows facile genetic exchange between viruses that co-infect the same host: through reassortment of intact gene segments, mixed infections frequently give rise to viral genotypes that differ from both parental strains [7]

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