DC-SIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from dendritic cells to T cells

Jean-François Arrighi, Marjorie Pion, Eduardo Garcia, Jean-Michel Escola, Yvette van Kooyk, Teunis B Geijtenbeek, Vincent Piguet

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Dendritic cells (DCs) are essential for the early events of human immunodeficiency virus (HIV) infection. Model systems of HIV sexual transmission have shown that DCs expressing the DC-specific C-type lectin DC-SIGN capture and internalize HIV at mucosal surfaces and efficiently transfer HIV to CD4+ T cells in lymph nodes, where viral replication occurs. Upon DC-T cell clustering, internalized HIV accumulates on the DC side at the contact zone (infectious synapse), between DCs and T cells, whereas HIV receptors and coreceptors are enriched on the T cell side. Viral concentration at the infectious synapse may explain, at least in part, why DC transmission of HIV to T cells is so efficient.Here, we have investigated the role of DC-SIGN on primary DCs in X4 HIV-1 capture and transmission using small interfering RNA-expressing lentiviral vectors to specifically knockdown DC-SIGN. We demonstrate that DC-SIGN- DCs internalize X4 HIV-1 as well as DC-SIGN+ DCs, although binding of virions is reduced. Strikingly, DC-SIGN knockdown in DCs selectively impairs infectious synapse formation between DCs and resting CD4+ T cells, but does not prevent the formation of DC-T cells conjugates. Our results demonstrate that DC-SIGN is required downstream from viral capture for the formation of the infectious synapse between DCs and T cells. These findings provide a novel explanation for the role of DC-SIGN in the transfer and enhancement of HIV infection from DCs to T cells, a crucial step for HIV transmission and pathogenesis.

Original languageEnglish
Pages (from-to)1279-88
Number of pages10
JournalJournal of Experimental Medicine
Issue number10
Publication statusPublished - 15 Nov 2004


  • Antibodies, Monoclonal
  • Binding Sites
  • Cell Adhesion Molecules/metabolism
  • Cells, Cultured
  • Dendritic Cells/metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Genetic Vectors
  • HIV Infections/metabolism
  • HIV-1/metabolism
  • Humans
  • Lectins, C-Type/metabolism
  • Lentivirus/genetics
  • Microscopy, Fluorescence
  • RNA, Small Interfering/genetics
  • Receptors, Cell Surface/metabolism
  • T-Lymphocytes/metabolism

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