DC-SIGN promotes Japanese encephalitis virus transmission from dendritic cells to T cells via virological synapses
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
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- Felts RL, Narayan K, Estes JD, Shi D, Trubey CM, Fu J, Hartnell LM, Ruthel GT, Schneider DK, Nagashima K, Bess JW, Bavari S, Lowekamp BC, Bliss D, Lifson JD, Subramaniam S 2010. 3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells. Proc Natl Acad Sci U S A, 107: 13336–13341.CrossRefPubMedPubMedCentralGoogle Scholar
- Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van Kooyk Y, Figdor CG. 2000a. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell, 100: 575–585.Google Scholar
- Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet H S, KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y. 2000. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell, 100: 587–597.CrossRefPubMedGoogle Scholar
- Halary F, Amara A, Lortat-Jacob H, Messerle M, Delaunay T, Houles C, Fieschi F, Arenzana-Seisdedos F, Moreau JF, Dechanet-Merville J. 2002. Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection. Immunity, 17: 653–664.CrossRefPubMedGoogle Scholar
- Norcross MA. 1984. A synaptic basis for T-lymphocyte activation. Ann Immunol (Paris), 135D: 113–134.Google Scholar
- Wang P, Hu K, Luo S, Zhang M, Deng X, Li C, Jin W, Hu B, He S, Li M, Du T, Xiao G, Zhang B, Liu Y, Hu Q. 2016. DC-SIGN as an attachment factor mediates Japanese encephalitis virus infection of human dendritic cells via interaction with a single high-mannose residue of viral E glycoprotein. Virology, 488: 108–119.CrossRefPubMedGoogle Scholar
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