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DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells

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(...

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Autores principales: Arrighi, Jean-François, Pion, Marjorie, Garcia, Eduardo, Escola, Jean-Michel, van Kooyk, Yvette, Geijtenbeek, Teunis B., Piguet, Vincent
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211914/
https://www.ncbi.nlm.nih.gov/pubmed/15545354
http://dx.doi.org/10.1084/jem.20041356
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author Arrighi, Jean-François
Pion, Marjorie
Garcia, Eduardo
Escola, Jean-Michel
van Kooyk, Yvette
Geijtenbeek, Teunis B.
Piguet, Vincent
author_facet Arrighi, Jean-François
Pion, Marjorie
Garcia, Eduardo
Escola, Jean-Michel
van Kooyk, Yvette
Geijtenbeek, Teunis B.
Piguet, Vincent
author_sort Arrighi, Jean-François
collection PubMed
description 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.
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spelling pubmed-22119142008-03-11 DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells Arrighi, Jean-François Pion, Marjorie Garcia, Eduardo Escola, Jean-Michel van Kooyk, Yvette Geijtenbeek, Teunis B. Piguet, Vincent J Exp Med Article 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. The Rockefeller University Press 2004-11-15 /pmc/articles/PMC2211914/ /pubmed/15545354 http://dx.doi.org/10.1084/jem.20041356 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Arrighi, Jean-François
Pion, Marjorie
Garcia, Eduardo
Escola, Jean-Michel
van Kooyk, Yvette
Geijtenbeek, Teunis B.
Piguet, Vincent
DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells
title DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells
title_full DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells
title_fullStr DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells
title_full_unstemmed DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells
title_short DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells
title_sort dc-sign–mediated infectious synapse formation enhances x4 hiv-1 transmission from dendritic cells to t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211914/
https://www.ncbi.nlm.nih.gov/pubmed/15545354
http://dx.doi.org/10.1084/jem.20041356
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