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HIV-1 trafficking to the dendritic cell-T-cell infectious synapse uses a pathway of tetraspanin sorting to the immunological synapse

Pelchen-Matthews, Annegret
Collinson, Lucy
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Published in Traffic. 2005, vol. 6, no. 6, p. 488-501
Abstract Dendritic cells (DCs) are essential components of the early events of HIV infection. Here, we characterized the trafficking pathways that HIV-1 follows during its capture by DCs and its subsequent presentation to CD4(+) T cells via an infectious synapse. Immunofluorescence microscopy indicates that the virus-containing compartment in mature DCs (mDCs) co-labels for the tetraspanins CD81, CD82, and CD9 but contains little CD63 or LAMP-1. Using ratio imaging of pH-reporting fluorescent virions in live DCs, we show that HIV-1 is internalized in an intracellular endocytic compartment with a pH of 6.2. Significantly, we demonstrate that the infectivity of cell-free virus is more stable at mildly acidic pH than at neutral pH. Using electron microscopy, we confirm that HIV-1 accumulates in intracellular vacuoles that contain CD81 positive internal membranes but overlaps only partially with CD63. When allowed to contact T cells, HIV-1-loaded DCs redistribute CD81, and CD9, as well as internalized HIV-1, but not the immunological synapse markers MHC-II and T-cell receptor to the infectious synapse. Together, our results indicate that HIV-1 is internalized into a non-conventional, non-lysosomal, endocytic compartment in mDCs and further suggest that HIV-1 is able to selectively subvert components of the intracellular trafficking machinery required for formation of the DC-T-cell immunological synapse to facilitate its own cell-to-cell transfer and propagation.
Keywords Antigens, CD/biosynthesisAntigens, CD63Antigens, CD81Antigens, CD82Antigens, CD9CD4-Positive T-Lymphocytes/immunologyCell SeparationCell-Free SystemCells, CulturedDendritic Cells/virologyEndocytosisEndosomes/metabolismFlow CytometryHIV-1/metabolismHumansHydrogen-Ion ConcentrationLysosome-Associated Membrane GlycoproteinsLysosomes/metabolismMembrane Glycoproteins/biosynthesisMembrane Proteins/metabolismMicroscopy, ElectronMicroscopy, FluorescenceMonocytes/cytologyPlatelet Membrane Glycoproteins/biosynthesisProto-Oncogene Proteins/biosynthesisT-Lymphocytes/virologyTemperatureTime Factors
PMID: 15882445
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Research group Signaux intracellulaires (210)
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GARCIA, Eduardo et al. HIV-1 trafficking to the dendritic cell-T-cell infectious synapse uses a pathway of tetraspanin sorting to the immunological synapse. In: Traffic, 2005, vol. 6, n° 6, p. 488-501. doi: 10.1111/j.1600-0854.2005.00293.x https://archive-ouverte.unige.ch/unige:30417

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Deposited on : 2013-10-16

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