Protective role for the N-terminal domain of α-dystroglycan in Influenza A virus proliferation.
Animals
Basement Membrane
/ drug effects
Body Fluids
/ drug effects
Cell Line
Cell Proliferation
/ drug effects
Dystroglycans
/ pharmacology
Glycosylation
/ drug effects
HEK293 Cells
Humans
Inflammation
/ drug therapy
Influenza A Virus, H1N1 Subtype
/ drug effects
Influenza, Human
/ drug therapy
Lung
/ drug effects
Mice
Mice, Inbred C57BL
Orthomyxoviridae Infections
/ drug therapy
Protective Agents
/ pharmacology
Viral Load
/ methods
inflammation
influenza A virus
α-dystroglycan
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
04 06 2019
04 06 2019
Historique:
pubmed:
18
5
2019
medline:
24
3
2020
entrez:
18
5
2019
Statut:
ppublish
Résumé
α-Dystroglycan (α-DG) is a highly glycosylated basement membrane receptor that is cleaved by the proprotein convertase furin, which releases its N-terminal domain (α-DGN). Before cleavage, α-DGN interacts with the glycosyltransferase LARGE1 and initiates functional O-glycosylation of the mucin-like domain of α-DG. Notably, α-DGN has been detected in a wide variety of human bodily fluids, but the physiological significance of secreted α-DGN remains unknown. Here, we show that mice lacking α-DGN exhibit significantly higher viral titers in the lungs after Influenza A virus (IAV) infection (strain A/Puerto Rico/8/1934 H1N1), suggesting an inability to control virus load. Consistent with this, overexpression of α-DGN before infection or intranasal treatment with recombinant α-DGN prior and during infection, significantly reduced IAV titers in the lungs of wild-type mice. Hemagglutination inhibition assays using recombinant α-DGN showed in vitro neutralization of IAV. Collectively, our results support a protective role for α-DGN in IAV proliferation.
Identifiants
pubmed: 31097590
pii: 1904493116
doi: 10.1073/pnas.1904493116
pmc: PMC6561248
doi:
Substances chimiques
Protective Agents
0
Dystroglycans
146888-27-9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11396-11401Subventions
Organisme : NIAID NIH HHS
ID : R01 AI042767
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI114543
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS053672
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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