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DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells
Open accessAbstract
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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“However, the results of other studies indicate the existence of a DC-SIGN-independent mechanism of trans-infection with HIV-1 viral particles [81,82,83,84].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [81]
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Metadata
- Authors
- Arrighi, J.-F., Pion, M., Garcia, E., Escola, J.-M., van Kooyk, Y., Geijtenbeek, T. B., & Piguet, V.
- Affiliations
- University Hospital of Geneva (CH)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Piguet, Vincent
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2004-11-15
- Volume
- 200
- Issue
- 10
- Pages
- 1279-1288
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2211914
- OpenAlex
- W2155011421
- Cited by
- 240
- References
- 51
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 6 · 2015: 11 · 2014: 14 · 2013: 11 · 2012: 20
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (67200, 68785)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- DC-SIGN, X4 HIV-1, dendritic cells, HIV transmission, CD4+ T cells, C-type lectin, viral capture, HIV co-receptor, HIV pathogenesis, mucosal HIV transmission
- MeSH terms
- DC-Specific ICAM-3 Grabbing Nonintegrin, Antibodies, Monoclonal, Binding Sites, Cells, Cultured, Dendritic Cells, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Genetic Vectors, Humans, Microscopy, Fluorescence, Receptors, Cell Surface, T-Lymphocytes, HIV-1, HIV Infections, Cell Adhesion Molecules, Lentivirus, RNA, Small Interfering, Lectins, C-Type
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