Details:

Alternative Title:
Nat Commun
Personal Author:
Flint, Mike ; Chatterjee, Payel ; Lin, David L. ; McMullan, Laura K. ; Shrivastava-Ranjan, Punya ; ... More +
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. Less -
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:
[+]
A549 Cells
Animals
Antiviral Agents
Article
Cathepsin B
Chlorocebus Aethiops
Clustered Regularly Interspaced Short Palindromic Repeats
Ebolavirus
Fibroblasts
Gene Knockout Techniques
Hemorrhagic Fever, Ebola
Humans
Mucolipidoses
Proprotein Convertases
Protease Inhibitors
Pyrrolidines
Serine Endopeptidases
Transferases (Other Substituted Phosphate Groups)
Vero Cells
Virus Internalization
Whole Genome Sequencing

Source:
Nat Commun. 10
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
R01 DK097374/DK/NIDDK NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:0547d24419bdab8eb65f22eea8a0e0ab609dc88f3647e0bd3dc0eb527af7b127
File Type:

Supporting Files

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