Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships

Abstract

The influenza A virus (IAV) genome consists of eight negative-sense viral RNA (vRNA) segments that are selectively assembled into progeny virus particles through RNA-RNA interactions. To explore putative intersegmental RNA-RNA relationships, we quantified similarity between phylogenetic trees comprising each vRNA segment from seasonal human IAV. Intersegmental tree similarity differed between subtype and lineage. While intersegmental relationships were largely conserved over time in H3N2 viruses, they diverged in H1N1 strains isolated before and after the 2009 pandemic. Surprisingly, intersegmental relationships were not driven solely by protein sequence, suggesting that IAV evolution could also be driven by RNA-RNA interactions. Finally, we used confocal microscopy to determine that colocalization of highly coevolved vRNA segments is enriched over other assembly intermediates at the nuclear periphery during productive viral infection. This study illustrates how putative RNA interactions underlying selective assembly of IAV can be interrogated with phylogenetics.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Scripts have been deposited to GitHub as described in the manuscript. Summary tables have been provided for Figures 2-7 and figure supplements.

The following previously published data sets were used

Article and author information

Author details

  1. Jennifer E Jones

    Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Valerie Le Sage

    Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Gabriella H Padovani

    Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael Calderon

    Cell Biology, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Erik S Wright

    Department of Biomedical Informatics, University of Pittsburgh, Madison, United States
    For correspondence
    eswright@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1457-4019
  6. Seema S Lakdawala

    Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    lakdawala@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7679-2150

Funding

National Institute of Allergy and Infectious Diseases (T32 AI049820)

  • Jennifer E Jones

Center for Evolutionary Biology and Medicine, University of Pittsburgh

  • Jennifer E Jones

National Institute of Allergy and Infectious Diseases (R01 AI139063)

  • Seema S Lakdawala

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

Reviewing Editor

  1. Imroze Khan, Ashoka University, India

Version history

  1. Preprint posted: January 14, 2021 (view preprint)
  2. Received: January 14, 2021
  3. Accepted: August 23, 2021
  4. Accepted Manuscript published: August 27, 2021 (version 1)
  5. Version of Record published: October 18, 2021 (version 2)

Copyright

© 2021, Jones et al.

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. Jennifer E Jones
  2. Valerie Le Sage
  3. Gabriella H Padovani
  4. Michael Calderon
  5. Erik S Wright
  6. Seema S Lakdawala
(2021)
Parallel evolution between genomic segments of seasonal human influenza viruses reveals RNA-RNA relationships
eLife 10:e66525.
https://doi.org/10.7554/eLife.66525

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https://doi.org/10.7554/eLife.66525

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