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

• Published in: Traffic (Copenhagen, Denmark) Vol. 12; no. 12; pp. 1702 - 1713
• Main Authors: Izquierdo‐Useros, Nuria, Esteban, Olga, Rodriguez‐Plata, Maria T., Erkizia, Itziar, Prado, Julia G., Blanco, Julià, García‐Parajo, Maria F., Martinez‐Picado, Javier
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2011
• Subjects: Biological Transport; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell Membrane - immunology; Cell Membrane - virology; Cell membranes; Cell-Free System; Cells, Cultured; Computed tomography; Cytoskeleton - immunology; Cytoskeleton - virology; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - virology; Endocytosis; Endocytosis - immunology; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; HIV‐1; Human immunodeficiency virus; Humans; Imaging, Three-Dimensional - methods; Kinetics; live cell imaging; Lymphocytes T; Lymphoid tissue; Microscopy; Microscopy, Video - methods; trans‐infection; Virion - immunology; Virus Attachment
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1111/j.1600-0854.2011.01281.x

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.