Dynamic Imaging of Cell-Free and Cell-Associated Viral Capture in Mature Dendritic Cells

Dynamic Imaging of Cell-Free and Cell-Associated Viral Capture in Mature Dendritic Cells

Fecha de publicación online: 10/10/2012 Fecha de publicación en papel: 12 Diciembre 2012 Revista: Traffic

Abstract:

Dendritic cells (DCs) capture human immunodeficiency virus (HIV) through a non-fusogenic mechanism that enables viral transmission to CD4+ T cells, contributing to in vivo viral dissemination. Although previous studies have provided important clues to cell-free viral capture by mature DCs (mDCs), dynamic and kinetic insight on this process is still missing. Here, we used three-dimensional video microscopy and single-particle tracking approaches to dynamically dissect both cell-free and cell-associated viral capture by living mDCs. We show that cell-free virus capture by mDCs operates through three sequential phases: virus binding through specific determinants expressed in the viral particle, polarized or directional movements toward concrete regions of the cell membrane and virus accumulation in a sac-like structure where trapped viral particles display a hindered diffusive behavior. Moreover, real-time imaging of cell-associated viral transfer to mDCs showed a similar dynamics to that exhibited by cell-free virus endocytosis leading to viral accumulation in compartments. However, cell-associated HIV type 1 transfer to mDCs was the most effective pathway, boosted throughout enhanced cellular contacts with infected CD4+ T cells. Our results suggest that in lymphoid tissues, mDC viral uptake could occur either by encountering cell-free or cell-associated virus produced by infected cells generating the perfect scenario to promote HIV pathogenesis and impact disease progression.

 

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Autores: Izquierdo-Useros N, Esteban O, Rodriguez-Plata MT, Erkizia I, Prado JG, Blanco J, García-Parajo MF, Martinez-Picado J.

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Irsi Caixa

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