DC-SIGN–mediated Infectious Synapse Formation Enhances X4 HIV-1 Transmission from Dendritic Cells to T Cells
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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.
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There exists a DC-SIGN-independent mechanism of trans-infection with HIV-1 viral particles.
“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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- 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)
- 2Department of Molecular Cell Biology and Immunology, VUMC, 1081 BT Amsterdam, Netherlands
- 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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