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

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 and Christina F. Spiropoulou ()
Additional contact information
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
Christina F. Spiropoulou: Centers for Disease Control and Prevention

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-08135-4

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