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Cited by 623HIV Research and TreatmentChemokine receptors and signalingT-cell and Retrovirus Studies

HIV-1 Cell to Cell Transfer across an Env-induced, Actin-dependent Synapse

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Jolly, Clare, Kashefi, Kirk, Hollinshead, Michael, Sattentau, Quentin J.·2004·The Journal of Experimental Medicine
DOI 10.1084/jem.20030648PMC PMC2211771
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Abstract

Direct cell–cell transfer is an efficient mechanism of viral dissemination within an infected host, and human immunodeficiency virus 1 (HIV-1) can exploit this mode of spread. Receptor recognition by HIV-1 occurs via interactions between the viral surface envelope glycoprotein (Env), gp120, and CD4 and a chemokine receptor, CCR5 or CXCR4. Here, we demonstrate that the binding of CXCR4-using HIV-1–infected effector T cells to primary CD4+/CXCR4+ target T cells results in rapid recruitment to the interface of CD4, CXCR4, talin, and lymphocyte function–associated antigen 1 on the target cell, and of Env and Gag on the effector cell. Recruitment of these membrane molecules into polarized clusters was dependent on Env engagement of CD4 and CXCR4 and required remodelling of the actin cytoskeleton. Transfer of Gag from effector to target cell was observed by 1 h after conjugate formation, was independent of cell–cell fusion, and was probably mediated by directed virion fusion with the target cell. We propose that receptor engagement by Env directs the rapid, actin-dependent recruitment of HIV receptors and adhesion molecules to the interface, resulting in a stable adhesive junction across which HIV infects the target cell.

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  • Other groups failed to detect HIV-1 endocytosis at the VS site by confocal or electron microscopy with tomography, indicating that virus enters target cells by fusion with the plasma membrane.

    “However, other groups failed to detect HIV-1 endocytosis at the VS site by confocal or electron microscopy with tomography, indicating that the virus enters target cells by fusion with the plasma membrane [35,53].”

    From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [35]

  • Virus transfer across the synaptic cleft occurs within 1-3 h, after which Gag is detected in the target cell.

    “Virus transfer across the synaptic cleft occurs within 1–3 h, after which Gag is detected in the target cell [35,40].”

    From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [35]

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Cited by

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Authors
Jolly, C., Kashefi, K., Hollinshead, M., & Sattentau, Q. J.
Affiliations
  • University of Oxford (GB)
  • Imperial College London (GB)
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2004-01-19
Volume
199
Issue
2
Pages
283-293
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20030648
PMC
PMC2211771
OpenAlex
W2143666216
Cited by
623
References
1
Citations by year
2026: 9 · 2025: 11 · 2024: 9 · 2023: 19 · 2022: 29 · 2021: 19 · 2020: 25 · 2019: 24 · 2018: 34 · 2017: 17 · 2016: 21 · 2015: 26 · 2014: 43 · 2013: 48 · 2012: 42
FWCI
10.83
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust (064018)
  • Department for International Development (G0100137)
  • Medical Research Council (G0100137)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords
HIV-1, cell-to-cell transmission, actin cytoskeleton, CXCR4, CD4, envelope glycoprotein, talin, LFA-1, viral dissemination, receptor engagement
MeSH terms
Actins, Cell Line, Humans, Intercellular Junctions, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, HIV Envelope Protein gp120, CD4 Antigens, Lymphocyte Function-Associated Antigen-1, Microscopy, Immunoelectron, Receptors, CXCR4

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