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

Article Article scientifique Article HIV-1 trafficking to the dendritic cell-T-cell infectious synapse uses a pathway of tetraspanin sorting to the immunological synapse eng 2005 author Garcia Eduardo 97093 author Pion Marjorie 556434 author Pelchen-Matthews Annegret author Collinson Lucy author Arrighi Jean-François 28404 author Blot Guillaume 593101 author Leuba Florence 96535 author Escola Jean-Michel 508297 author Demaurex Nicolas 0000-0002-9933-6772 24642 author Marsh Mark author Piguet Vincent 84926 488-501 10.1111/j.1600-0854.2005.00293.x 15882445 1398-9219 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. Antigens, CD/biosynthesis Antigens, CD63 Antigens, CD81 Antigens, CD82 Antigens, CD9 CD4-Positive T-Lymphocytes/immunology Cell Separation Cell-Free System Cells, Cultured Dendritic Cells/virology Endocytosis Endosomes/metabolism Flow Cytometry HIV-1/metabolism Humans Hydrogen-Ion Concentration Lysosome-Associated Membrane Glycoproteins Lysosomes/metabolism Membrane Glycoproteins/biosynthesis Membrane Proteins/metabolism Microscopy, Electron Microscopy, Fluorescence Monocytes/cytology Platelet Membrane Glycoproteins/biosynthesis Proto-Oncogene Proteins/biosynthesis T-Lymphocytes/virology Temperature Time Factors Dewey 612 Dewey 616 54 Département de microbiologie et médecine moléculaire 21B 134 Département de physiologie cellulaire et métabolisme 21C false 168 Signaux intracellulaires 210 Traffic 6 6 3947edcb-1fff-4800-b481-2dd75995067d Article (Published version) Restricted HIV-1 trafficking to the dendritic.pdf 4176915 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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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	Traffic			2005	743	0

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Blot, Guillaume