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How antibodies alter the cell entry pathway of dengue virus particles in macrophages
- Source :
- Scientific Reports, Scientific Reports, 6. NLM (Medline), Scientific Reports, 6:28768. Nature Publishing Group
- Publication Year :
- 2016
-
Abstract
- Antibody-dependent enhancement of dengue virus (DENV) infection plays an important role in the exacerbation of DENV-induced disease. To understand how antibodies influence the fate of DENV particles, we explored the cell entry pathway of DENV in the absence and presence of antibodies in macrophage-like P388D1 cells. Recent studies unraveled that both mature and immature DENV particles contribute to ADE, hence, both particles were studied. We observed that antibody-opsonized DENV enters P388D1 cells through a different pathway than non-opsonized DENV. Antibody-mediated DENV entry was dependent on FcγRs, pH, Eps15, dynamin, actin, PI3K, Rab5 and Rab7. In the absence of antibodies, DENV cell entry was FcγR, PI3K and Rab5-independent. Live-cell imaging of fluorescently-labeled particles revealed that actin-mediated membrane protrusions facilitate virus uptake. In fact, actin protrusions were found to actively search and capture antibody-bound virus particles distantly located from the cell body, a phenomenon that is not observed in the absence of antibodies. Overall, similar results were seen for antibody-opsonized standard and antibody-bound immature DENV preparations, indicating that the maturation status of the virus does not control the entry pathway. Collectively, our findings suggest that antibodies alter the cell entry pathway of DENV and trigger a novel mechanism of initial virus-cell contact.
- Subjects :
- 0301 basic medicine
Viral pathogenesis
viruses
Cell
Dengue virus
medicine.disease_cause
Dengue
Mice
LINE P388D1
INFECTION ENHANCEMENT
Multidisciplinary
biology
virus diseases
CLATHRIN-MEDIATED ENDOCYTOSIS
Endocytosis
Cell biology
Actin Cytoskeleton
medicine.anatomical_structure
Antibody
DYNAMIN
Virus
Antibodies
Article
PHAGOCYTOSIS
ACTIN
Cell Line
03 medical and health sciences
INDEPENDENT ENDOCYTOSIS
medicine
Animals
Humans
PI3K/AKT/mTOR pathway
Dynamin
COMPLEX
dengue virus
viral pathogenesis
Macrophages
Cell Membrane
Receptors, IgG
Receptor-mediated endocytosis
FC-GAMMA-RECEPTOR
biochemical phenomena, metabolism, and nutrition
Dengue Virus
Virus Internalization
Virology
Antibody-Dependent Enhancement
Kinetics
030104 developmental biology
Culicidae
biology.protein
DEPENDENT ENHANCEMENT
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....9a135cefbd7312c72995c7ec5f4f9dd7