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A complement component C1q-mediated mechanism of antibody-dependent enhancement of Ebola virus infection
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 14, Iss 9, p e0008602 (2020)
- Publication Year :
- 2020
- Publisher :
- Public Library of Science, 2020.
-
Abstract
- 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.<br />Author summary Ebola virus (EBOV) utilizes the complement component C1q for antibody-dependent enhancement (ADE) of infection. We found that an ADE antibody increased viral attachment in the presence of C1q and that there was no significant difference in the efficiency of viral 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 for endocytosis. These results suggest that C1q-mediated ADE of EBOV infection is simply caused by increased viral attachment to the cell surface, most likely via cross-linking of virus-antibody-C1q complexes to cellular C1q receptors.
- Subjects :
- 0301 basic medicine
RNA viruses
Physiology
viruses
RC955-962
Fc receptor
Cancer Treatment
medicine.disease_cause
Pathology and Laboratory Medicine
Antibodies, Viral
Biochemistry
Tyrosine Kinases
0302 clinical medicine
Cell Signaling
Arctic medicine. Tropical medicine
Immune Physiology
Tyrosine Kinase Signaling Cascade
Chlorocebus aethiops
Medicine and Health Sciences
Immune System Proteins
Membrane Glycoproteins
biology
Chemistry
Pinocytosis
Antibodies, Monoclonal
Ebolavirus
Signaling Cascades
Endocytosis
Cell biology
Enzymes
Receptors, Complement
Infectious Diseases
Oncology
Vesicular stomatitis virus
Medical Microbiology
Vesicular Stomatitis Virus
Filoviruses
Viral Pathogens
Viruses
Public aspects of medicine
RA1-1270
Pathogens
Cellular Structures and Organelles
Ebola Virus
Research Article
Signal Transduction
Signal Inhibition
030231 tropical medicine
Immunology
Virus Attachment
chemical and pharmacologic phenomena
Endosomes
Microbiology
Virus
Antibodies
Rhabdoviruses
Cell Line
03 medical and health sciences
Viral Proteins
Antibody Therapy
Viral entry
medicine
Animals
Humans
Antibody-dependent enhancement
Vesicles
Microbial Pathogens
Vero Cells
Ebola virus
Biology and life sciences
Hemorrhagic Fever Viruses
Complement C1q
Public Health, Environmental and Occupational Health
Organisms
Proteins
Cell Biology
Hemorrhagic Fever, Ebola
biology.organism_classification
Antibody-Dependent Enhancement
030104 developmental biology
HEK293 Cells
biology.protein
Enzymology
Clinical Immunology
Clinical Medicine
Protein Kinases
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 14
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....e77354c34a694da760463d2bed8c972e