Virologica Sinica

, Volume 32, Issue 6, pp 495–502 | Cite as

DC-SIGN promotes Japanese encephalitis virus transmission from dendritic cells to T cells via virological synapses

  • Ping Wang
  • Mei Li
  • Wei Lu
  • Di Zhang
  • Qinxue Hu
  • Yalan LiuEmail author
Research Article


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.


Japanese 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).

Author Contributions

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.

Supplementary material

12250_2017_4034_MOESM1_ESM.pdf (2.2 mb)
DC-SIGN promotes Japanese encephalitis virus transmission from dendritic cells to T cells via virological synapses


  1. Aleyas AG, George JA, Han YW, Rahman MM, Kim SJ, Han SB, Kim BS, Kim K, Eo SK. 2009. Functional modulation of dendritic cells and macrophages by Japanese encephalitis virus through MyD88 adaptor molecule-dependent and -independent pathways. J Immunol, 183: 2462–2474.CrossRefGoogle Scholar
  2. Arrighi JF, Pion M, Garcia E, Escola JM, van Kooyk Y, Geijtenbeek TB, Piguet V. 2004. DC-SIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from dendritic cells to T cells. J Exp Med, 200: 1279–1288.CrossRefGoogle Scholar
  3. Dale BM, McNerney GP, Thompson DL, Hubner W, de Los Reyes K, Chuang FY, Huser T, Chen BK. 2011. Cell-to-cell transfer of HIV-1 via virological synapses leads to endosomal virion maturation that activates viral membrane fusion. Cell Host Microbe, 10: 551–562.CrossRefGoogle Scholar
  4. de Witte L, de Vries RD, van der Vlist M, Yuksel S, Litjens M, de Swart RL, Geijtenbeek TB. 2008. DC-SIGN and CD150 have distinct roles in transmission of measles virus from dendritic cells to T-lymphocytes. PLoS Pathog, 4: e1000049.CrossRefGoogle Scholar
  5. Diamond MS, Shrestha B, Mehlhop E, Sitati E, Engle M. 2003. Innate and adaptive immune responses determine protection against disseminated infection by West Nile encephalitis virus. Viral Immunol, 16: 259–278.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. Figdor CG, van Kooyk Y, Adema GJ. 2002. C-type lectin receptors on dendritic cells and Langerhans cells. Nat Rev Immunol, 2: 77–84.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. Iwasaki Y, Zhao JX, Yamamoto T, Konno H. 1986. Immunohistochemical demonstration of viral antigens in Japanese encepha-litis. Acta Neuropathol, 70: 79–81.CrossRefGoogle Scholar
  12. Jin W, Li C, Du T, Hu K, Huang X, Hu Q. 2014. DC-SIGN plays a stronger role than DCIR in mediating HIV-1 capture and transfer. Virology, 458-459: 83–92.CrossRefGoogle Scholar
  13. Li C, Jin W, Du T, Wu B, Liu Y, Shattock RJ, Hu Q. 2014. Binding of HIV-1 virions to alpha4beta 7 expressing cells and impact of antagonizing alpha4beta 7 on HIV-1 infection of primary CD4+T cells. Virol Sin, 29: 381–392.CrossRefGoogle Scholar
  14. Malissen B, Tamoutounour S, Henri S. 2014. The origins and functions of dendritic cells and macrophages in the skin. Nat Rev Immunol, 14: 417–428.CrossRefGoogle Scholar
  15. Mathur A, Kulshreshtha R, Chaturvedi UC. 1989. Evidence for latency of Japanese encephalitis virus in T lymphocytes. J Gen Virol, 70(Pt 2): 461–465.CrossRefGoogle Scholar
  16. Mathur A, Arora KL, Rawat S, Chaturvedi UC. 1986. Persistence, latency and reactivation of Japanese encephalitis virus infection in mice. J Gen Virol, 67(Pt 2): 381–385.CrossRefGoogle Scholar
  17. Norcross MA. 1984. A synaptic basis for T-lymphocyte activation. Ann Immunol (Paris), 135D: 113–134.Google Scholar
  18. Paul WE, Brown M, Hornbeck P, Mizuguchi J, Ohara J, Rabin E, Snapper C, Tsang W. 1987. Regulation of B-lymphocyte activation, proliferation, and differentiation. Ann N Y Acad Sci, 505: 82–89.CrossRefGoogle Scholar
  19. Pierson T C, Kielian M. 2013. Flaviviruses: braking the entering. Curr Opin Virol, 3: 3–12.CrossRefGoogle Scholar
  20. Ren X X, Ma L, Liu Q W, Li C, Huang Z, Wu L, Xiong SD, Wang JH, Wang HB. 2014. The molecule of DC-SIGN captures enterovirus 71 and confers dendritic cell-mediated viral trans-infection. Virol J, 11: 47.CrossRefGoogle Scholar
  21. Sharma S, Mathur A, Prakash V, Kulshreshtha R, Kumar R, Chaturvedi UC. 1991. Japanese encephalitis virus latency in peripheral blood lymphocytes and recurrence of infection in children. Clin Exp Immunol, 85: 85–89.CrossRefGoogle Scholar
  22. Shimauchi T, Piguet V. 2015. DC-T cell virological synapses and the skin: novel perspectives in dermatology. Exp Dermatol, 24: 1–4.CrossRefGoogle Scholar
  23. van den Hurk AF, Ritchie SA, Mackenzie JS. 2009. Ecology and geographical expansion of Japanese encephalitis virus. Annu Rev Entomol, 54: 17–35.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.State Key Laboratory of Virology, Wuhan Institute of VirologyChinese Academy of SciencesWuhanChina
  2. 2.University of Chinese Academy of SciencesBeijingChina
  3. 3.Institute for Infection and ImmunitySt George’s University of LondonLondonUK
  4. 4.Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical CollegeHuazhong University of Science & TechnologyWuhanChina

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