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.

Back to Previous Page

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:

[+]

File Type:

Supporting Files:

	41467_2018_8135_Fig5_HTML.gif	image/gif
	41467_2018_8135_Fig5_HTML.jpg	image/jpeg
	41467_2018_8135_Fig6_HTML.gif	image/gif
	41467_2018_8135_Fig6_HTML.jpg	image/jpeg
	41467_2018_8135_Fig7_HTML.gif	image/gif
	41467_2018_8135_Fig7_HTML.jpg	image/jpeg
	41467_2018_8135_MOESM1_ESM.pdf	application/pdf
	41467_2018_8135_MOESM2_ESM.pdf	application/pdf
	41467_2018_8135_MOESM3_ESM.docx	application/vnd.openxmlformats-officedocument.wordprocessingml.document
	41467_2018_8135_MOESM4_ESM.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
	41467_2018_8135_Fig1_HTML.gif	image/gif
	41467_2018_8135_MOESM5_ESM.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
	41467_2018_8135_MOESM6_ESM.pdf	application/pdf
	41467_2018_Article_8135.nxml	text/xml
	41467_2018_8135_Fig1_HTML.jpg	image/jpeg
	41467_2018_8135_Fig2_HTML.gif	image/gif
	41467_2018_8135_Fig2_HTML.jpg	image/jpeg
	41467_2018_8135_Fig3_HTML.gif	image/gif
	41467_2018_8135_Fig3_HTML.jpg	image/jpeg
	41467_2018_8135_Fig4_HTML.gif	image/gif
	41467_2018_8135_Fig4_HTML.jpg	image/jpeg

No Related Documents.

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

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

You May Also Like:

Have Questions?

CDC INFORMATION

CONNECT WITH CDC