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How antibodies alter the cell entry pathway of dengue virus particles in macrophages.

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.

SUBMITTER: Ayala-Nunez NV

PROVIDER: S-EPMC4935958 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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How antibodies alter the cell entry pathway of dengue virus particles in macrophages.

Ayala-Nunez Nilda V NV Hoornweg Tabitha E TE van de Pol Denise P I DP Sjollema Klaas A KA Flipse Jacky J van der Schaar Hilde M HM Smit Jolanda M JM

Scientific reports 20160707

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 ce ...[more]

PMID: 27385443

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How antibodies alter the cell entry pathway of dengue virus particles in macrophages.

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How antibodies alter the cell entry pathway of dengue virus particles in macrophages.

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