1. Cell Biology

Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells

  1. Enric Gutiérrez-Martínez
  2. Susana Benet Garrab
  3. Nicolas Mateos
  4. Itziar Erkiziac
  5. Jon Ander Nieto-Garai
  6. Maier Lorizate
  7. Kyra JE Borgman
  8. Carlo Manzo
  9. Felix Campelo
  10. Nuria Izquierdo-Useros  Is a corresponding author
  11. Javier Martinez-Picado  Is a corresponding author
  12. Maria F Garcia-Parajo  Is a corresponding author
  1. The Barcelona Institute of Science and Technology, Spain
  2. Hospital Universitari Germans Trias i Pujol, Spain
  3. IrsiCaixa AIDS Research Institute, Spain
  4. Universidad del País Vasco (UPV/EHU), Spain
  5. Universitat Central de Catalunya, Spain
https://doi.org/10.7554/eLife.78836
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Cite this article
  1. Enric Gutiérrez-Martínez
  2. Susana Benet Garrab
  3. Nicolas Mateos
  4. Itziar Erkiziac
  5. Jon Ander Nieto-Garai
  6. Maier Lorizate
  7. Kyra JE Borgman
  8. Carlo Manzo
  9. Felix Campelo
  10. Nuria Izquierdo-Useros
  11. Javier Martinez-Picado
  12. Maria F Garcia-Parajo
(2023)
Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells
eLife 12:e78836.
https://doi.org/10.7554/eLife.78836
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  3. Download .RIS

Abstract

The immunoglobulin-like lectin receptor CD169 (Siglec-1) mediates the capture of HIV-1 by activated dendritic cells (DC) through binding to sialylated ligands. These interactions result in a more efficient virus capture as compared to resting DCs, although the underlying mechanisms are poorly understood. Using a combination of super-resolution microscopy, single particle tracking and biochemical perturbations we studied the nanoscale organization of Siglec-1 on activated DCs and its impact on viral capture and its trafficking to a single viral-containing compartment. We found that activation of DCs leads to Siglec-1 basal nanoclustering at specific plasma membrane regions where receptor diffusion is constrained by Rho-ROCK activation and formin-dependent actin polymerization. Using liposomes with varying ganglioside concentrations, we further demonstrate that Siglec-1 nanoclustering enhances the receptor avidity to limiting concentrations of gangliosides carrying sialic ligands. Binding to either HIV-1 particles or ganglioside-bearing liposomes lead to enhanced Siglec-1 nanoclustering and global actin rearrangements characterized by a drop in RhoA activity, facilitating the final accumulation of viral particles in a single sac-like compartment. Overall, our work provides new insights on the role of the actin machinery of activated DCs in regulating the formation of basal Siglec-1 nanoclustering, being decisive for the capture and actin-dependent trafficking of HIV-1 into the virus-containing compartment.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1-6 and for the corresponding figure supplements.

Article and author information

Author details

  1. Enric Gutiérrez-Martínez

    Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    No competing interests declared.

  2. Susana Benet Garrab

    Infectious Diseases Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
    Competing interests
    No competing interests declared.

  3. Nicolas Mateos

    Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    No competing interests declared.

  4. Itziar Erkiziac

    IrsiCaixa AIDS Research Institute, Badalona, Spain
    Competing interests
    No competing interests declared.

  5. Jon Ander Nieto-Garai

    Universidad del País Vasco (UPV/EHU), Bilbao, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8665-099X

  6. Maier Lorizate

    Universidad del País Vasco (UPV/EHU), Bilbao, Spain
    Competing interests
    No competing interests declared.

  7. Kyra JE Borgman

    Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7898-2911

  8. Carlo Manzo

    Facultat de Ciències i Tecnologia, Universitat Central de Catalunya, Vic, Spain
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8625-0996

  9. Felix Campelo

    Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Barcelona, Spain
    Competing interests
    Felix Campelo, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0786-9548

  10. Nuria Izquierdo-Useros

    IrsiCaixa AIDS Research Institute, Badalona, Spain
    For correspondence
    nizquierdo@irsicaixa.es
    Competing interests
    Nuria Izquierdo-Useros, declares patent applications related to the inhibition of viral interactions with Siglec-1. application reference EP23382072.9. The author declare no other competing interests.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1039-1821

  11. Javier Martinez-Picado

    IrsiCaixa AIDS Research Institute, Badalona, Spain
    For correspondence
    jmpicado@irsicaixa.es
    Competing interests
    Javier Martinez-Picado, declares patent applications related to the inhibition of viral interactions with Siglec-1. application reference EP23382072.9. The author declare no other competing interests.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4916-2129

  12. Maria F Garcia-Parajo

    Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Barcelona, Spain
    For correspondence
    maria.garcia-parajo@icfo.eu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6618-3944

Funding

European Research Council (788546)

  • Maria F Garcia-Parajo

Spanish National Plan for Scientific and Technical Research and Innovation (PID2020-117145RB-I00)

  • Nuria Izquierdo-Useros

Generalitat de Catalunya (2017SGR1000)

  • Maria F Garcia-Parajo

FUNDACIÓ Privada MIR-PUIG

  • Maria F Garcia-Parajo

Fundación Cellex

  • Maria F Garcia-Parajo

European Commission (754558)

  • Nicolas Mateos

Spanish National Plan for Scientific and Technical Research and Innovation (CEX2019-000910-S)

  • Maria F Garcia-Parajo

Spanish National Plan for Scientific and Technical Research and Innovation (PID2020-113068RB-I00 / 10.13039/501100011033)

  • Maria F Garcia-Parajo

Spanish National Plan for Scientific and Technical Research and Innovation (PID2019-109870RB-I00)

  • Javier Martinez-Picado

Spanish National Plan for Scientific and Technical Research and Innovation (PID2020-117405GB-100)

  • Maier Lorizate

Spanish National Plan for Scientific and Technical Research and Innovation (RYC-2017-22227)

  • Felix Campelo

Spanish National Plan for Scientific and Technical Research and Innovation (RYC-2015-17896)

  • Carlo Manzo

Spanish National Plan for Scientific and Technical Research and Innovation (PID2019-106232RB-I00/10.13039/501100011033)

  • Felix Campelo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mark Marsh, University College London, United Kingdom

Version history

  1. Received: March 22, 2022
  2. Preprint posted: April 30, 2022 (view preprint)
  3. Accepted: March 19, 2023
  4. Accepted Manuscript published: March 20, 2023 (version 1)
  5. Version of Record published: March 31, 2023 (version 2)

Copyright

© 2023, Gutiérrez-Martínez et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Enric Gutiérrez-Martínez
  2. Susana Benet Garrab
  3. Nicolas Mateos
  4. Itziar Erkiziac
  5. Jon Ander Nieto-Garai
  6. Maier Lorizate
  7. Kyra JE Borgman
  8. Carlo Manzo
  9. Felix Campelo
  10. Nuria Izquierdo-Useros
  11. Javier Martinez-Picado
  12. Maria F Garcia-Parajo
(2023)
Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells
eLife 12:e78836.
https://doi.org/10.7554/eLife.78836

Share this article

https://doi.org/10.7554/eLife.78836

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