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

Flint, Mike; Chatterjee, Payel; Lin, David L.; McMullan, Laura K.; Shrivastava-Ranjan, Punya; Bergeron, Éric; Lo, Michael K.; Welch, Stephen R.; Nichol, Stuart T.; Tai, Andrew W.; Spiropoulou, Christina F.

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

Published Date:

January 17 2019

Source:

Nat Commun. 10

Language:

English

[PDF-1.75 MB]

Details:

Alternative Title:

Nat Commun

Personal Author:

Flint, Mike ; Chatterjee, Payel ; Lin, David L. ; McMullan, Laura K. ; Shrivastava-Ranjan, Punya ; ... More ▼

Description:

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.

Subject:

[+]

Pubmed ID:

30655525

Pubmed Central ID:

PMC6336797

Document Type:

Journal Article

Funding:

R01 DK097374/DK/NIDDK NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ;

Collection(s):

CDC Public Access

Main Document Checksum:

[+]

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