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

Research output: Contribution to journalArticleAcademicpeer-review

199 Citations (Scopus)

Abstract

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
Volume200
Issue number10
DOIs
Publication statusPublished - 15 Nov 2004

Keywords

  • 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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