Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry.
Biological Transport
Carrier Proteins
/ metabolism
Ebolavirus
/ genetics
Endosomes
/ metabolism
Filoviridae
/ genetics
Filoviridae Infections
/ genetics
Glycoproteins
/ metabolism
Hemorrhagic Fever, Ebola
/ metabolism
Host-Pathogen Interactions
Membrane Glycoproteins
/ metabolism
Niemann-Pick C1 Protein
/ metabolism
Protein Transport
/ genetics
Receptors, Virus
/ metabolism
Tumor Suppressor Proteins
/ genetics
Viral Envelope Proteins
/ genetics
Virus Internalization
/ drug effects
Ebola virus
filovirus
vesicular trafficking
virus entry
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
30 07 2020
30 07 2020
Historique:
received:
21
05
2020
accepted:
23
05
2020
pubmed:
5
6
2020
medline:
7
1
2021
entrez:
5
6
2020
Statut:
epublish
Résumé
Ebola virus (EBOV) entry requires internalization into host cells and extensive trafficking through the endolysosomal network in order to reach late endosomal/lysosomal compartments that contain triggering factors for viral membrane fusion. These triggering factors include low-pH-activated cellular cathepsin proteases, which cleave the EBOV glycoprotein (GP), exposing a domain which binds to the filoviral receptor, the cholesterol transporter Niemann-Pick C1 (NPC1). Here, we report that trafficking of EBOV to NPC1 requires expression of the homotypic fusion and protein sorting (HOPS) tethering complex as well as its regulator, UV radiation resistance-associated gene (UVRAG). Using an inducible clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, we demonstrated that depletion of HOPS subunits as well as UVRAG impairs entry by all pathogenic filoviruses. UVRAG depletion resulted in reduced delivery of EBOV virions to NPC1
Identifiants
pubmed: 32493822
pii: JVI.01002-20
doi: 10.1128/JVI.01002-20
pmc: PMC7394885
pii:
doi:
Substances chimiques
Carrier Proteins
0
Glycoproteins
0
Membrane Glycoproteins
0
Niemann-Pick C1 Protein
0
Receptors, Virus
0
Tumor Suppressor Proteins
0
UVRAG protein, human
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CIHR
ID : ER1143489352509
Pays : Canada
Organisme : CIHR
ID : PJT155984390487
Pays : Canada
Informations de copyright
Copyright © 2020 Bo et al.
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