HIV-1-infected blood mononuclear cells form an integrin- and agrin-dependent viral synapse to induce efficient HIV-1 transcytosis across epithelial cell monolayer

Entrée Muqueuse du VIH et Immunité muqueuse, Departement de Biologie Cellulaire, Institut Cochin, CNRS, INSERM, Université René Descartes, 75014 Paris, France.
Molecular Biology of the Cell (Impact Factor: 4.47). 10/2005; 16(9):4267-79. DOI: 10.1091/mbc.E05-03-0192
Source: PubMed


The heparan sulfate proteoglycan agrin and adhesion molecules are key players in the formation of neuronal and immune synapses that evolved for efficient communication at the sites of cell-cell contact. Transcytosis of infectious virus across epithelial cells upon contact between HIV-1-infected cells and the mucosal pole of the epithelial cells is one mechanism for HIV-1 entry at mucosal sites. In contrast, transcytosis of cell-free HIV-1 is not efficient. A synapse between HIV-1-infected cells and the mucosal epithelial surface that resembles neuronal and immune synapses is visualized by electron microscopy. We have termed this the "viral synapse." Similarities of the viral synapse also extend to the functional level. HIV-1-infected cell-induced transcytosis depends on RGD-dependent integrins and efficient cell-free virus transcytosis is inducible upon RGD-dependent integrin cross-linking. Agrin appears differentially expressed at the apical epithelial surface and acts as an HIV-1 attachment receptor. Envelope glycoprotein subunit gp41 binds specifically to agrin, reinforcing the interaction of gp41 to its epithelial receptor galactosyl ceramide.

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Available from: Annette Alfsen, Oct 18, 2015
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    • "HIV spreading in cell culture has also been observed to be resistant to neutralizing antibodies and to the antiviral drug tenofovir, which efficiently inhibit cell-free HIV [12], [20], [23], [24]. The current concept to explain these observations can be described by the virological synapse, a virus-induced synaptic-like contact between infected cells and uninfected target cells [23], [25], [26], [27], [28], [29], [30], [31]. The virological synapse is believed to efficiently coordinate several steps of the viral life cycle [1], [3], [4]. "
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    • "Moreover, the transmitted virus was able to infect human DCs located immediately below the epithelial barrier (Martin-Latil et al., 2012). HIV-1 has also been shown to be capable of crossing intact oral and intestinal epithelial barriers by transcytosis and to be capable of infecting DCs, macrophages, and CD4+ T cells on the other side of those barriers in both ex vivo studies using tissue explants and in vitro studies (Bomsel, 1997; Alfsen et al., 2005; Tugizov et al., 2012). "
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    • "In contrast to cell-free HIV-1 infection, cell-associated infection arises from direct cell-to-cell transfer of virus to susceptible target cells. Cell-to-cell spread of HIV-1 in culture is significantly more efficient than spread of cell-free virus and involves formation of a transient yet complex virological synapse [14]–[17], which is more difficult to neutralize [15]. "
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