Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses

• Published in: Nature communications 2013-10, Vol.4 (1), p.2636-2636, Article 2636
• Main Authors: Wilker, Peter R., Dinis, Jorge M., Starrett, Gabriel, Imai, Masaki, Hatta, Masato, Nelson, Chase W., O’Connor, David H., Hughes, Austin L., Neumann, Gabriele, Kawaoka, Yoshihiro, Friedrich, Thomas C.
• Format: Article
• Language: English
• Subjects: 631/326/596/2563; 692/699/255/1578; Acids; Adaptation, Biological; Animals; Avian flu; Ferrets - virology; Genetic diversity; Hemagglutinin Glycoproteins, Influenza Virus - genetics; High-Throughput Nucleotide Sequencing; Host Specificity; Host-Pathogen Interactions; Humanities and Social Sciences; Humans; Infections; Influenza A Virus, H5N1 Subtype - genetics; Medical research; multidisciplinary; Mutation; Orthomyxoviridae Infections - transmission; Orthomyxoviridae Infections - veterinary; Orthomyxoviridae Infections - virology; Pandemics; Polymorphism, Single Nucleotide; Reassortant Viruses - genetics; Science; Science (multidisciplinary); Selection, Genetic; Species Specificity; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms3636

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. Mutations in the haemagglutinin of H5N1 avian influenza viruses confer transmissibility in ferrets. Here, Wilker et al . show that while within host variability is high, transmitted virus diversity is low suggesting a genetic bottleneck acts during transmission, driven by selection on haemagglutinin genes.