A complement component C1q-mediated mechanism of antibody-dependent enhancement of Ebola virus infection.
Animals
Antibodies, Monoclonal
/ immunology
Antibodies, Viral
/ immunology
Antibody-Dependent Enhancement
/ immunology
Cell Line
Chlorocebus aethiops
Complement C1q
/ metabolism
Ebolavirus
/ immunology
Endocytosis
/ immunology
HEK293 Cells
Hemorrhagic Fever, Ebola
/ immunology
Humans
Membrane Glycoproteins
/ metabolism
Receptors, Complement
/ metabolism
Vero Cells
Viral Proteins
/ immunology
Virus Attachment
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
12
11
2019
accepted:
14
07
2020
revised:
17
09
2020
pubmed:
5
9
2020
medline:
29
10
2020
entrez:
4
9
2020
Statut:
epublish
Résumé
Besides the common Fc receptor (FcR)-mediated mechanism of antibody-dependent enhancement (ADE), Ebola virus (EBOV) is known to utilize the complement component C1q for ADE of infection. This mechanism is FcR-independent and mediated by cross-linking of virus-antibody-C1q complexes to cell surface C1q receptors, leading to enhanced viral entry into cells. Using confocal microscopy, we found that virus-like particles (VLPs) consisting of EBOV glycoprotein, nucleoprotein, and matrix protein attached to the surface of human kidney 293 cells more efficiently in the presence of an ADE monoclonal antibody and C1q than with the antibody or C1q alone, and that there was no significant difference in the efficiency of VLP uptake into endosomes between the C1q-mediated ADE and non-ADE entry. Accordingly, both ADE and non-ADE infection were similarly decreased by inhibitors of the signaling pathways known to be required for endocytosis. These results suggest that C1q-mediated ADE of EBOV infection is simply caused by increased attachment of virus particles to the cell surface, which is distinct from the mechanism of FcR-mediated ADE requiring intracellular signaling to promote phagocytosis/macropinocytosis.
Identifiants
pubmed: 32886656
doi: 10.1371/journal.pntd.0008602
pii: PNTD-D-19-01921
pmc: PMC7497997
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Viral
0
Membrane Glycoproteins
0
Receptors, Complement
0
Viral Proteins
0
complement 1q receptor
0
Complement C1q
80295-33-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0008602Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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