β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway.
ADP-Ribosylation Factors
/ metabolism
Animals
COVID-19
/ metabolism
Female
HeLa Cells
Heterocyclic Compounds, 2-Ring
/ pharmacology
Humans
Lysosomes
Mice
SARS-CoV-2
/ metabolism
Secretory Pathway
Thiourea
/ analogs & derivatives
Virus Release
rab GTP-Binding Proteins
/ antagonists & inhibitors
rab7 GTP-Binding Proteins
COVID-19 Drug Treatment
CD1067700
Rab7
SARS-CoV-2
acidification/deacidification ARL8b
antigen presentation
coronavirus
lysosome
pH
viral egress
viral immunology
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
10 12 2020
10 12 2020
Historique:
received:
14
07
2020
revised:
11
09
2020
accepted:
22
10
2020
pubmed:
7
11
2020
medline:
22
12
2020
entrez:
6
11
2020
Statut:
ppublish
Résumé
β-Coronaviruses are a family of positive-strand enveloped RNA viruses that includes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much is known regarding their cellular entry and replication pathways, but their mode of egress remains uncertain. Using imaging methodologies and virus-specific reporters, we demonstrate that β-coronaviruses utilize lysosomal trafficking for egress rather than the biosynthetic secretory pathway more commonly used by other enveloped viruses. This unconventional egress is regulated by the Arf-like small GTPase Arl8b and can be blocked by the Rab7 GTPase competitive inhibitor CID1067700. Such non-lytic release of β-coronaviruses results in lysosome deacidification, inactivation of lysosomal degradation enzymes, and disruption of antigen presentation pathways. β-Coronavirus-induced exploitation of lysosomal organelles for egress provides insights into the cellular and immunological abnormalities observed in patients and suggests new therapeutic modalities.
Identifiants
pubmed: 33157038
pii: S0092-8674(20)31446-X
doi: 10.1016/j.cell.2020.10.039
pmc: PMC7590812
pii:
doi:
Substances chimiques
ARL8B protein, human
0
Arl8B protein, mouse
0
CID1067700
0
Heterocyclic Compounds, 2-Ring
0
rab7 GTP-Binding Proteins
0
rab7 GTP-binding proteins, human
0
rab7 GTP-binding proteins, mouse
0
ADP-Ribosylation Factors
EC 3.6.5.2
rab GTP-Binding Proteins
EC 3.6.5.2
Thiourea
GYV9AM2QAG
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1520-1535.e14Subventions
Organisme : NINDS NIH HHS
ID : R01 NS036592
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI035370
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI091985
Pays : United States
Organisme : NIAID NIH HHS
ID : F32 AI113973
Pays : United States
Organisme : NIGMS NIH HHS
ID : R37 GM058615
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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