DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist.
Animals
Antigens, CD
/ metabolism
COVID-19
/ prevention & control
Cell Adhesion Molecules
/ metabolism
Cell Line
Chlorocebus aethiops
Humans
Jurkat Cells
Lectins, C-Type
/ metabolism
Lung
/ metabolism
Mannose-Binding Lectins
/ metabolism
Mannosides
/ pharmacology
Protein Binding
/ drug effects
Receptors, Cell Surface
/ metabolism
Respiratory Mucosa
/ metabolism
SARS-CoV-2
/ metabolism
Spike Glycoprotein, Coronavirus
/ metabolism
Vero Cells
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
17
11
2020
accepted:
20
04
2021
entrez:
20
5
2021
pubmed:
21
5
2021
medline:
1
6
2021
Statut:
epublish
Résumé
The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.
Identifiants
pubmed: 34015061
doi: 10.1371/journal.ppat.1009576
pii: PPATHOGENS-D-20-02496
pmc: PMC8136665
doi:
Substances chimiques
Antigens, CD
0
CD207 protein, human
0
CLEC4M protein, human
0
Cell Adhesion Molecules
0
DC-specific ICAM-3 grabbing nonintegrin
0
Lectins, C-Type
0
MGL lectin, human
0
Mannose-Binding Lectins
0
Mannosides
0
Receptors, Cell Surface
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009576Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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