title: The infectious synapse formed between mature dendritic cells and CD4(+) T cells is independent of the presence of the HIV-1 envelope glycoprotein.
abstract: BACKGROUND
  Since cell-mediated infection of human immunodeficiency virus type 1 (HIV-1) is more efficient than cell-free infection, cell-to-cell propagation plays a crucial role in the pathogenesis of HIV-1 infection. Transmission of HIV-1 is enabled by two types of cellular contacts, namely, virological synapses between productively infected cells and uninfected target cells and infectious synapses between uninfected dendritic cells (DC) harboring HIV-1 and uninfected target cells. While virological synapses are driven by expression of the viral envelope glycoprotein on the cell surface, little is known about the role of envelope glycoprotein during contact between DC and T cells. We explored the contribution of HIV-1 envelope glycoprotein, adhesion molecules, and antigen recognition in the formation of conjugates comprising mature DC (mDC) and CD4(+) T cells in order to further evaluate their role in mDC-mediated HIV-1 transmission at the immunological synapse.
  
  
  RESULTS
  Unlike virological synapse, HIV-1 did not modulate the formation of cell conjugates comprising mDC harboring HIV-1 and non-activated primary CD4(+) T cells. Disruption of interactions between ICAM-1 and LFA-1, however, resulted in a 60% decrease in mDC-CD4(+) T-cell conjugate formation and, consequently, in a significant reduction of mDC-mediated HIV-1 transmission to non-activated primary CD4(+) T cells (p < 0.05). Antigen recognition or sustained MHC-TcR interaction did not enhance conjugate formation, but significantly boosted productive mDC-mediated transmission of HIV-1 (p < 0.05) by increasing T-cell activation and proliferation.
  
  
  CONCLUSIONS
  Formation of the infectious synapse is independent of the presence of the HIV-1 envelope glycoprotein, although it does require an interaction between ICAM-1 and LFA-1. This interaction is the main driving force behind the formation of mDC-CD4(+) T-cell conjugates and enables transmission of HIV-1 to CD4(+) T cells. Moreover, antigen recognition boosts HIV-1 replication without affecting the frequency of cellular conjugates. Our results suggest a determinant role for immune activation driven by mDC-CD4(+) T-cell contacts in viral dissemination and that this activation likely contributes to the pathogenesis of HIV-1 infection.
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, 08916, Spain.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Rodriguez-Plata
authors.forename: Isabel
authors.initials: I
authors.lastname: Puigdomènech
authors.forename: Nuria
authors.initials: N
authors.lastname: Izquierdo-Useros
authors.forename: Maria C
authors.initials: MC
authors.lastname: Puertas
authors.forename: Jorge
authors.initials: J
authors.lastname: Carrillo
authors.forename: Itziar
authors.initials: I
authors.lastname: Erkizia
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Julià
authors.initials: J
authors.lastname: Blanco
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000821:virology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D053586:Virus Internalization; D054299:env Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D054299:env Gene Products, Human Immunodeficiency Virus; D018799:Intercellular Adhesion Molecule-1