期刊
TRAFFIC
卷 12, 期 12, 页码 1702-1713出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1600-0854.2011.01281.x
关键词
dendritic cells; HIV-1; live cell imaging; trans-infection
类别
资金
- Spanish Ministry of Education and Science [SAF2007-64696, SAF2010-21224, MAT2007-66629-C02-01]
- Spanish AIDS network 'Red Tematica Cooperativa de Investigacion en SIDA' [RD06/0006]
- Catalan HIV Vaccine Development Program (HIVACAT)
- Generalitat de Catalunya [2009 SRG 597]
- [BES-2008-002609]
- ICREA Funding Source: Custom
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 videomicroscopy 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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