1. Epidemiology and Global Health
  2. Microbiology and Infectious Disease
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Viral factors in influenza pandemic risk assessment

  1. Marc Lipsitch  Is a corresponding author
  2. Wendy Barclay
  3. Rahul Raman
  4. Charles J Russell
  5. Jessica A Belser
  6. Sarah Cobey
  7. Peter M Kasson
  8. James O Lloyd-Smith
  9. Sebastian Maurer-Stroh
  10. Steven Riley
  11. Catherine AA Beauchemin
  12. Trevor Bedford
  13. Thomas C Friedrich
  14. Andreas Handel
  15. Sander Herfst
  16. Pablo R Murcia
  17. Benjamin Roche
  18. Claus O Wilke
  19. Colin A Russell
  1. Harvard TH Chan School of Public Health, United States
  2. Imperial College London, United Kingdom
  3. Massachusetts Institute of Technology, United States
  4. St Jude Children's Research Hospital, United States
  5. Centers for Disease Control and Prevention, United States
  6. University of Chicago, United States
  7. University of Virginia, United States
  8. University of California, Los Angeles, United States
  9. Agency for Science, Technology and Research, Singapore
  10. Ryerson University, Canada
  11. Fred Hutchinson Cancer Research Center, United States
  12. University of Wisconsin School of Veterinary Medicine, United States
  13. University of Georgia, United States
  14. Erasmus Medical Center, Netherlands
  15. MRC-University of Glasgow Centre For Virus Research, United Kingdom
  16. Institut de Recherche pour le Développement, France
  17. The University of Texas at Austin, United States
  18. University of Cambridge, United Kingdom
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Cite this article as: eLife 2016;5:e18491 doi: 10.7554/eLife.18491

Abstract

The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk.

Article and author information

Author details

  1. Marc Lipsitch

    Center for Communicable Disease Dynamics, Departments of Epidemiology and Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, United States
    For correspondence
    mlipsitc@hsph.harvard.edu
    Competing interests
    Marc Lipsitch, ML reports the following financial disclosures for topics unrelated to this manuscript: consulting income from Pfizer and Affinivax (both donated to charity) and research funding from Pfizer and PATH Vaccine Solutions. These entities had no role in the preparation of this work or in the decision to submit the work for publicationReviewing editor for eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1504-9213
  2. Wendy Barclay

    Division of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  3. Rahul Raman

    Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Charles J Russell

    Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, United States
    Competing interests
    No competing interests declared.
  5. Jessica A Belser

    Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, United States
    Competing interests
    No competing interests declared.
  6. Sarah Cobey

    Department of Ecology and Evolutionary Biology, University of Chicago, Chicago, United States
    Competing interests
    No competing interests declared.
  7. Peter M Kasson

    Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  8. James O Lloyd-Smith

    Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7941-502X
  9. Sebastian Maurer-Stroh

    Bioinformatics Institute, Agency for Science, Technology and Research, Singapore, Singapore
    Competing interests
    No competing interests declared.
  10. Steven Riley

    MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  11. Catherine AA Beauchemin

    Department of Physics, Ryerson University, Toronto, Canada
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0599-0069
  12. Trevor Bedford

    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    No competing interests declared.
  13. Thomas C Friedrich

    Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, United States
    Competing interests
    No competing interests declared.
  14. Andreas Handel

    University of Georgia, Athens, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4622-1146
  15. Sander Herfst

    Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    No competing interests declared.
  16. Pablo R Murcia

    MRC-University of Glasgow Centre For Virus Research, Glasgow, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4352-394X
  17. Benjamin Roche

    UMI UMMISCO, Institut de Recherche pour le Développement, Montpellier, France
    Competing interests
    No competing interests declared.
  18. Claus O Wilke

    Department of Integrative Biology, The University of Texas at Austin, Austin, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7470-9261
  19. Colin A Russell

    Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    Colin A Russell, During the prepartion of this manuscript, CAAB received funding through aresearch contract with AstraZeneca Inc., but for distinct, unrelatedresearch. AstraZeneca Inc. had no role in the preparation of this work orin the decision to submit the work for publication..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2113-162X

Funding

National Health and Medical Research Council (12/1/06/24/5793)

  • Sebastian Maurer-Stroh

Wellcome (200861/Z/16/Z)

  • Steven Riley

Medical Research Council (MR/J008761/1)

  • Steven Riley

National Institute of General Medical Sciences (MIDAS U01 GM110721-01)

  • Steven Riley

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (VIDI grant 91715372)

  • Sander Herfst

Agency for Science, Technology and Research (12/1/06/24/5793)

  • Sebastian Maurer-Stroh

National Institute of Allergy and Infectious Diseases (Centers of Excellence for Influenza Research and Surveillance (Contract HHSN272201400006C))

  • Charles J Russell

National Institutes of Health (R01 GM088344)

  • Claus O Wilke

National Institutes of Health (R01 GM098304)

  • Peter M Kasson

Royal Society (University Research Fellowship)

  • Colin A Russell

Medical Research Council (G0801822)

  • Pablo R Murcia

Wellcome (Project 093488/Z/10/Z)

  • Steven Riley

Wellcome (200187/Z/15/Z)

  • Steven Riley

National Institute of General Medical Sciences (MIDAS Center of Excellence Cooperative Agreement U54GM088558)

  • Marc Lipsitch

Natural Sciences and Engineering Research Council of Canada (Discovery Grant (355837-2013))

  • Catherine AA Beauchemin

Ministry of Research and Innovation (Early Researcher Award Award (ER13-09-040))

  • Catherine AA Beauchemin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Yi Guan, University of Hong Kong, Hong Kong

Publication history

  1. Received: June 9, 2016
  2. Accepted: November 3, 2016
  3. Accepted Manuscript published: November 11, 2016 (version 1)
  4. Version of Record published: December 14, 2016 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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Further reading

    1. Epidemiology and Global Health
    Allison Koenecke et al.
    Short Report

    In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺1-AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺1-AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺1-AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.

    1. Epidemiology and Global Health
    Evangelos Evangelou et al.
    Research Article Updated

    Background:

    Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample.

    Methods:

    We assessed global effect sizes of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta, and liver of UK Biobank participants who reported drinking alcohol.

    Results:

    We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (–1.7 × 10−3 ± 0.76 × 10−3 per doubling of alcohol consumption, p=3.0 × 10−14). Alcohol consumption was also associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption.

    Conclusions:

    Our results imply that there is not a ‘safe threshold’ below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.

    Funding:

    See acknowledgements.