HIV-1-infected blood mononuclear cells form an integrin- and agrin-dependent viral synapse to induce efficient HIV-1 transcytosis across epithelial cell monolayer.
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.
Entrée Muqueuse du VIH et Immunité muqueuse, Departement de Biologie Cellulaire, Institut Cochin, CNRS, INSERM, Université René Descartes, 75014 Paris, France.
Annette
A
Alfsen
Huifeng
H
Yu
Aude
A
Magérus-Chatinet
Alain
A
Schmitt
Morgane
M
Bomsel
D018171:Agrin / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D019483:Disintegrins / Q000502:physiology; D004847:Epithelial Cells / Q000648:ultrastructure / Q000821:virology*; D005699:Galactosylceramides / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D037102:Lectins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000648:ultrastructure / Q000821:virology*; D015398:Signal Transduction / Q000502:physiology; D054301:gag Gene Products, Human Immunodeficiency Virus
D018171:Agrin; D019483:Disintegrins; D005699:Galactosylceramides; D015683:Gene Products, gag; D019812:Heparan Sulfate Proteoglycans; D019012:Integrin beta1; D037102:Lectins; D054301:gag Gene Products, Human Immunodeficiency Virus; C083868:gag protein p1, Human immunodeficiency virus