title: Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses.
abstract: The emergence of human-transmissible H5N1 avian influenza viruses poses a major pandemic threat. H5N1 viruses are thought to be highly genetically diverse both among and within hosts; however, the effects of this diversity on viral replication and transmission are poorly understood. Here we use deep sequencing to investigate the impact of within-host viral variation on adaptation and transmission of H5N1 viruses in ferrets. We show that, although within-host genetic diversity in haemagglutinin (HA) increases during replication in inoculated ferrets, HA diversity is dramatically reduced upon respiratory droplet transmission, in which infection is established by only 1-2 distinct HA segments from a diverse source virus population in transmitting animals. Moreover, minor HA variants present in as little as 5.9% of viruses within the source animal become dominant in ferrets infected via respiratory droplets. These findings demonstrate that selective pressures acting during influenza virus transmission among mammals impose a significant bottleneck.
authors.affiliation: 1] Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, Wisconsin 53706, USA [2] [3].
authors.forename: Peter R
authors.initials: PR
authors.lastname: Wilker
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Dinis
authors.forename: Gabriel
authors.initials: G
authors.lastname: Starrett
authors.forename: Masaki
authors.initials: M
authors.lastname: Imai
authors.forename: Masato
authors.initials: M
authors.lastname: Hatta
authors.forename: Chase W
authors.initials: CW
authors.lastname: Nelson
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Austin L
authors.initials: AL
authors.lastname: Hughes
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D005289:Ferrets / Q000821:virology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D058507:Host Specificity; D054884:Host-Pathogen Interactions; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000635:transmission* / Q000662:veterinary* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D016865:Reassortant Viruses / Q000235:genetics*; D012641:Selection, Genetic; D013045:Species Specificity
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus