title: Human immunodeficiency virus type-1 infection impairs the formation of the immunological synapse.
abstract: HIV-1-infected lymphocytes improperly respond to T cell antigen receptor (TCR) stimulation. To document this phenomenon, we studied the capacity of HIV-1-infected lymphocytes to form immunological synapses. We show here that HIV-1-infected T cells poorly conjugated with antigen-presenting cells, and when they formed conjugates, the synapses were abnormal. TCR and Lck accumulated in the recycling endosomal compartment, and their clustering at the synapse was severely reduced. These phenomena were, to a large extent, caused by Nef, a viral protein affecting intracellular trafficking and signaling pathways. Concomitantly, in HIV-infected cells, tyrosine phosphorylation at the synapse and the patterns of tyrosine phosphorylated proteins were disturbed in a Nef-dependent manner. These findings underscore the importance of Lck and TCR endosomal trafficking in synapse formation and early T cell signaling. Alteration of endocytic and signaling networks at the immunological synapse likely impacts the function and fate of HIV-1-infected cells.
authors.affiliation: Unité de Biologie Cellulaire des Lymphocytes, Centre National de la Recherche Scientifique Unité de Recherche Associée-1930, Institut Pasteur, 25-28 rue Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Thoulouze
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sol-Foulon
authors.forename: Fabien
authors.initials: F
authors.lastname: Blanchet
authors.forename: Alice
authors.initials: A
authors.lastname: Dautry-Varsat
authors.forename: Olivier
authors.initials: O
authors.lastname: Schwartz
authors.forename: Andrés
authors.initials: A
authors.lastname: Alcover
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015693:Gene Products, nef / Q000276:immunology / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D021381:Protein Transport / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D011948:Receptors, Antigen, T-Cell; D054311:nef Gene Products, Human Immunodeficiency Virus; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)