Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses
Open Access
- 23 October 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 4 (1), 2636
- https://doi.org/10.1038/ncomms3636
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.This publication has 45 references indexed in Scilit:
- A tale of three next generation sequencing platforms: comparison of Ion torrent, pacific biosciences and illumina MiSeq sequencersBMC Genomics, 2012
- Low-Abundance Drug-Resistant Viral Variants in Chronically HIV-Infected, Antiretroviral Treatment–Naive Patients Significantly Impact Treatment OutcomesThe Journal of Infectious Diseases, 2009
- Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infectionProceedings of the National Academy of Sciences of the United States of America, 2008
- Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of MicePLoS Pathogens, 2007
- The viral polymerase mediates adaptation of an avian influenza virus to a mammalian hostProceedings of the National Academy of Sciences of the United States of America, 2005
- Emerging Influenza Viruses: Past and PresentCurrent Molecular Medicine, 2005
- Molecular Signatures of Natural SelectionAnnual Review of Genetics, 2005
- Probable Person-to-Person Transmission of Avian Influenza A (H5N1)The New England Journal of Medicine, 2005
- RNA VIRUS MUTATIONS AND FITNESS FOR SURVIVALAnnual Review of Microbiology, 1997
- Receptor determinants of human and animal influenza virus isolates: Differences in receptor specificity of the H3 hemagglutinin based on species of originVirology, 1983