The infectious synapse formed between mature dendritic cells and CD4 + T cells is independent of the presence of the HIV-1 envelope glycoprotein
Rodriguez-Plata, Maria T. (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Puigdomènech Iñiguez, Isabel (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Izquierdo Useros, Nuria (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Puertas, Maria C.. (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Carrillo, Jorge (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Erkizia, Itziar (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Blanco, Julià (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martínez Picado, Francisco Javier (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Universitat Autònoma de Barcelona

Fecha:	2013
Resumen:	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. 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. 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.
Ayudas:	Ministerio de Ciencia e Innovación SAF2010-21224 Ministerio de Ciencia e Innovación BES-2008-002609 Instituto de Salud Carlos III CD09-0231
Nota:	Altres ajuts:This work was supported the Spanish AIDS Network (RD06/0006), the Catalan HIV Vaccine Development Program (HIVACAT), and the Spanish Foundation for AIDS Research and Prevention (FIPSE) project 36750/08.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Infectious synapse ; Virological synapse ; Immunological synapse ; Dendritic cell ; CD4 + T cell ; Cell-to-cell ; HIV-1 ; Trans -infection ; Transmission
Publicado en:	Retrovirology, Vol. 10 (april 2013) , p. 42, ISSN 1742-4690

DOI: 10.1186/1742-4690-10-42
PMID: 23590845

16 p, 1.9 MB

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