DC-SIGN promotes Japanese encephalitis virus transmission from dendritic cells to T cells via virological synapses
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Skin-resident dendritic cells (DCs) likely encounter incoming viruses in the first place, and their migration to lymph nodes following virus capture may promote viral replication. However, the molecular mechanisms underlying these processes remain unclear. In the present study, we found that compared to cell-free viruses, DC-bound viruses showed enhanced capture of JEV by T cells. Additionally, JEV infection was increased by co-culturing DCs and T cells. Blocking the C-type lectin receptor DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) with neutralizing antibodies or antagonists blocked JEV transmission to T cells. Live-cell imaging revealed that DCs captured and transferred JEV viral particles to T cells via virological synapses formed at DC-T cell junctions. These findings indicate that DC-SIGN plays an important role in JEV transmission from DCs to T cells and provide insight into how JEV exploits the migratory and antigen-presenting capabilities of DCs to gain access to lymph nodes for dissemination and persistence in the host.
KeywordsJapanese encephalitis virus (JEV) DC-SIGN T lymphocytes in trans
This work was supported by the National Key Research and Development Program of China (2016YFC1200400), the National Natural Science Foundation of China Grants (81572009 and 31570165) and the National High Technology Research and Development Program of China (2014AA021406). We thank the Core Facility and Technical Support at Wuhan Institute of Virology for technique supports of Confocal Microscopy (Dr. Ding Gao) and Flow Cytometry (Ms. Juan Min).
PW performed the major experiments and statistical analysis, drafted and revised the manuscript. ML, WL and DZ participated in the statistical analysis and revised the manuscript. QXH and YLL designed the study, drafted and revised the manuscript. All authors read and approved the final manuscript.
Compliance with Ethics Guidelines
The authors declare that they have no competing interests. All protocols involving human blood samples were reviewed and approved by the Local Research Ethics Committee. Informed written consents from the human subjects were obtained in this study.
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