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Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells.
Gutiérrez-Martínez, Enric; Benet Garrabé, Susana; Mateos, Nicolas; Erkizia, Itziar; Nieto-Garai, Jon Ander; Lorizate, Maier; Borgman, Kyra J E; Manzo, Carlo; Campelo, Felix; Izquierdo-Useros, Nuria; Martinez-Picado, Javier; Garcia-Parajo, Maria F.
Affiliation
  • Gutiérrez-Martínez E; ICFO - Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Benet Garrabé S; Lluita contra la sida foundation, Infectious Diseases Department, Hospital Germans Trias i Pujol, Badalona, Spain.
  • Mateos N; ICFO - Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Erkizia I; IrsiCaixa AIDS Research Institute, Badalona, Spain.
  • Nieto-Garai JA; Department of Biochemistry and Molecular Biology, Universidad del País Vasco, Bilbao, Spain.
  • Lorizate M; Department of Biochemistry and Molecular Biology, Universidad del País Vasco, Bilbao, Spain.
  • Borgman KJE; ICFO - Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Manzo C; Facultat de Ciències i Tecnologia, Universitat de Vic - Universitat Central de Catalunya, Vic, Spain.
  • Campelo F; ICFO - Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Izquierdo-Useros N; IrsiCaixa AIDS Research Institute, Badalona, Spain.
  • Martinez-Picado J; Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain.
  • Garcia-Parajo MF; CIBER de enfermedades infecciosas, Madrid, Spain.
Elife ; 122023 03 20.
Article in En | MEDLINE | ID: mdl-36940134
The immunoglobulin-like lectin receptor CD169 (Siglec-1) mediates the capture of HIV-1 by activated dendritic cells (DCs) 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV-1 Limits: Humans Language: En Journal: Elife Year: 2023 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV-1 Limits: Humans Language: En Journal: Elife Year: 2023 Document type: Article Affiliation country: Country of publication: