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A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus

Author

Listed:
  • Mike Flint

    (Centers for Disease Control and Prevention)

  • Payel Chatterjee

    (Centers for Disease Control and Prevention)

  • David L. Lin

    (University of Michigan Medical School)

  • Laura K. McMullan

    (Centers for Disease Control and Prevention)

  • Punya Shrivastava-Ranjan

    (Centers for Disease Control and Prevention)

  • Éric Bergeron

    (Centers for Disease Control and Prevention)

  • Michael K. Lo

    (Centers for Disease Control and Prevention)

  • Stephen R. Welch

    (Centers for Disease Control and Prevention)

  • Stuart T. Nichol

    (Centers for Disease Control and Prevention)

  • Andrew W. Tai

    (University of Michigan Medical School
    University of Michigan Medical School)

  • Christina F. Spiropoulou

    (Centers for Disease Control and Prevention)

Abstract

There are no approved therapies for Ebola virus infection. Here, to find potential therapeutic targets, we perform a screen for genes essential for Ebola virus (EBOV) infection. We identify GNPTAB, which encodes the α and β subunits of N-acetylglucosamine-1-phosphate transferase. We show that EBOV infection of a GNPTAB knockout cell line is impaired, and that this is reversed by reconstituting GNPTAB expression. Fibroblasts from patients with mucolipidosis II, a disorder associated with mutations in GNPTAB, are refractory to EBOV, whereas cells from their healthy parents support infection. Impaired infection correlates with loss of the expression of cathepsin B, known to be essential for EBOV entry. GNPTAB activity is dependent upon proteolytic cleavage by the SKI-1/S1P protease. Inhibiting this protease with the small-molecule PF-429242 blocks EBOV entry and infection. Disruption of GNPTAB function may represent a strategy for a host-targeted therapy for EBOV.

Suggested Citation

  • Mike Flint & Payel Chatterjee & David L. Lin & Laura K. McMullan & Punya Shrivastava-Ranjan & Éric Bergeron & Michael K. Lo & Stephen R. Welch & Stuart T. Nichol & Andrew W. Tai & Christina F. Spiropo, 2019. "A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08135-4
    DOI: 10.1038/s41467-018-08135-4
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    Cited by:

    1. Vanessa Monteil & Hyesoo Kwon & Lijo John & Cristiano Salata & Gustav Jonsson & Sabine U. Vorrink & Sofia Appelberg & Sonia Youhanna & Matheus Dyczynski & Alexandra Leopoldi & Nicole Leeb & Jennifer V, 2023. "Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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