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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    • "It is plausible that other mechanism(s) are involved in HTLV-1 infection across the gut epithelial barrier due to the low infectivity of cell-free virus. While cell-free HIV-1 is generally thought to be much more infectious than cell-free HTLV-1, it has been suggested that HIV-1-infected lymphocytes more efficiently infect target cells in the gut than cell-free virus – possibly through the formation of a viral synapse that induces transcytosis[117]. The role of the virological synapse in these transmission events has not been carefully studied. "
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    • "Despite the fact that many have observed that cell-associated virus can migrate across epithelial barriers[55,58,67,76,85,97], the mechanism of how this occurs is still unknown. The cell-associated viral migration observed in our study was not simply due to 'fitter' virus or T cell contact, suggesting that there may be a " synapse " that occurs between HIV infected lymphocytes and epithelial cells that facilitates the uptake and/or migration process , a mechanism that has been proposed by others[67,87]. CT infection of A2EN cells may enhance this " synaptic " process, allowing more virions to gain access to the basolateral compartment . "
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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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