Distinct functional determinants of influenza hemagglutinin-mediated membrane fusion

  1. Tijana Ivanovic  Is a corresponding author
  2. Stephen C Harrison
  1. Brandeis University, United States
  2. Harvard Medical School, United States

Abstract

Membrane fusion is the critical step for infectious cell penetration by enveloped viruses. We have previously used single-virion measurements of fusion kinetics to study the molecular mechanism of influenza-virus envelope fusion. Published data on fusion inhibition by antibodies to the 'stem' of influenza virus hemagglutinin (HA) now allow us to incorporate into simulations the provision that some HAs are inactive. We find that more than half of the HAs are unproductive even for virions with no bound antibodies, but that the overall mechanism is extremely robust. Determining the fraction of competent HAs allows us to determine their rates of target-membrane engagement. Comparison of simulations with data from H3N2 and H1N1 viruses reveals three independent functional variables of HA-mediated membrane fusion closely linked to neutralization susceptibility. Evidence for compensatory changes in the evolved mechanism sets the stage for studies aiming to define the molecular constraints on HA evolvability.

Article and author information

Author details

  1. Tijana Ivanovic

    Department of Biochemistry, Brandeis University, Waltham, United States
    For correspondence
    ivanovic@brandeis.edu
    Competing interests
    No competing interests declared.
  2. Stephen C Harrison

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    Stephen C Harrison, Reviewing editor, eLife.

Reviewing Editor

  1. Axel T Brunger, Stanford University, United States

Version history

  1. Received: August 20, 2015
  2. Accepted: November 26, 2015
  3. Accepted Manuscript published: November 27, 2015 (version 1)
  4. Version of Record published: February 3, 2016 (version 2)

Copyright

© 2015, Ivanovic & Harrison

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Tijana Ivanovic
  2. Stephen C Harrison
(2015)
Distinct functional determinants of influenza hemagglutinin-mediated membrane fusion
eLife 4:e11009.
https://doi.org/10.7554/eLife.11009

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https://doi.org/10.7554/eLife.11009

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