Viral-induced alternative splicing of host genes promotes influenza replication

  1. Matthew G Thompson
  2. Mark Dittmar
  3. Michael J Mallory
  4. Prasanna Bhat
  5. Max B Ferretti
  6. Beatriz MA Fontoura
  7. Sara Cherry
  8. Kristen W Lynch  Is a corresponding author
  1. University of Pennsylvania, United States
  2. UT Southwestern Medical Center, United States

Abstract

Viral infection induces the expression of numerous host genes that impact the outcome of infection. Here we show that infection of human lung epithelial cells with Influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. While these splicing-regulated genes are not enriched for canonical regulators of viral infection, we find that many of these genes do impact replication of IAV. Moreover, in several cases, specific inhibition of the IAV-induced splicing pattern also attenuates viral infection. We further show that approximately a quarter of the IAV-induced splicing events are regulated by hnRNP K, a host protein required for efficient splicing of the IAV M transcript in nuclear speckles. Finally, we find an increase in hnRNP K in nuclear speckles upon IAV infection, which may alter accessibility of hnRNP K for host transcripts thereby leading to a program of host splicing changes that promote IAV replication.

Data availability

Sequencing data have been deposited in GEO under accession code GSE142499

The following data sets were generated

Article and author information

Author details

  1. Matthew G Thompson

    Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Mark Dittmar

    Pathology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael J Mallory

    Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Prasanna Bhat

    Cell Biology, UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Max B Ferretti

    Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Beatriz MA Fontoura

    Cell Biology, UT Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Sara Cherry

    Pathology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Kristen W Lynch

    Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States
    For correspondence
    klync@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0120-8079

Funding

National Institutes of Health (R35 GM118048)

  • Matthew G Thompson
  • Michael J Mallory
  • Max B Ferretti
  • Kristen W Lynch

National Institutes of Health (R01 AI125524)

  • Matthew G Thompson
  • Prasanna Bhat
  • Beatriz MA Fontoura
  • Kristen W Lynch

National Institutes of Health (R01 AI150246,R01 AI122749,R01 AI140539)

  • Mark Dittmar
  • Sara Cherry

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

Reviewing Editor

  1. Douglas L Black, University of California, Los Angeles, United States

Version history

  1. Received: January 27, 2020
  2. Accepted: December 2, 2020
  3. Accepted Manuscript published: December 3, 2020 (version 1)
  4. Version of Record published: December 14, 2020 (version 2)

Copyright

© 2020, Thompson 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. Matthew G Thompson
  2. Mark Dittmar
  3. Michael J Mallory
  4. Prasanna Bhat
  5. Max B Ferretti
  6. Beatriz MA Fontoura
  7. Sara Cherry
  8. Kristen W Lynch
(2020)
Viral-induced alternative splicing of host genes promotes influenza replication
eLife 9:e55500.
https://doi.org/10.7554/eLife.55500

Share this article

https://doi.org/10.7554/eLife.55500

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