IFITM3 directly engages and shuttles incoming virus particles to lysosomes.
A549 Cells
Animals
Antigens, Differentiation
/ metabolism
Antiviral Agents
Endosomes
/ physiology
HeLa Cells
Humans
Lysosomes
/ physiology
Membrane Proteins
/ metabolism
Optical Imaging
/ methods
Protein Transport
RNA-Binding Proteins
/ metabolism
Transport Vesicles
/ physiology
Virion
/ pathogenicity
Virus Internalization
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
16
11
2017
accepted:
03
12
2018
pubmed:
16
1
2019
medline:
20
4
2019
entrez:
16
1
2019
Statut:
ppublish
Résumé
Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live-cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, IFITM2 and IFITM3 act cooperatively and function in a dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live-cell imaging studies, we show that IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live-cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation.
Identifiants
pubmed: 30643282
doi: 10.1038/s41589-018-0213-2
pii: 10.1038/s41589-018-0213-2
pmc: PMC6466627
mid: NIHMS1515781
doi:
Substances chimiques
Antigens, Differentiation
0
Antiviral Agents
0
IFITM2 protein, human
0
IFITM3 protein, human
0
Membrane Proteins
0
RNA-Binding Proteins
0
leu-13 antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
259-268Subventions
Organisme : NIAID NIH HHS
ID : R01 AI091707
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM087544
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134824
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI088027
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI156674
Pays : United States
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