Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells
- The Barcelona Institute of Science and Technology, Spain
- Hospital Universitari Germans Trias i Pujol, Spain
- IrsiCaixa AIDS Research Institute, Spain
- Universidad del País Vasco (UPV/EHU), Spain
- Universitat Central de Catalunya, Spain
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
Jon Ander Nieto-Garai
Nuria Izquierdo-Useros
Javier Martinez-Picado
Maria F Garcia-Parajo
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.
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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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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