TY - JOUR T1 - Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells JF - bioRxiv DO - 10.1101/2022.04.28.489919 SP - 2022.04.28.489919 AU - Enric Gutiérrez-Martínez AU - Susana Benet AU - Nicolas Mateos AU - Itziar Erkizia AU - Jon Ander Nieto-Garai AU - Maier Lorizate AU - Carlo Manzo AU - Felix Campelo AU - Nuria Izquierdo-Useros AU - Javier Martinez-Picado AU - Maria F. Garcia-Parajo Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/04/30/2022.04.28.489919.abstract N2 - 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.Competing Interest StatementThe authors have declared no competing interest. ER -