title: Dynamic imaging of cell-free and cell-associated viral capture in mature dendritic cells.
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.
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Izquierdo-Useros
authors.forename: Olga
authors.initials: O
authors.lastname: Esteban
authors.forename: Maria T
authors.initials: MT
authors.lastname: Rodriguez-Plata
authors.forename: Itziar
authors.initials: I
authors.lastname: Erkizia
authors.forename: Julia G
authors.initials: JG
authors.lastname: Prado
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
authors.forename: Maria F
authors.initials: MF
authors.lastname: García-Parajo
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
mesh_terms: D001692:Biological Transport; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002462:Cell Membrane / Q000276:immunology / Q000821:virology; D002474:Cell-Free System; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D004705:Endocytosis / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D018715:Microscopy, Video / Q000379:methods; D014771:Virion / Q000276:immunology*; D053585:Virus Attachment