title: Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells.
abstract: Plasmacytoid dendritic cells (pDCs) constitute a major source of type-I interferon (IFN-I) production during acute HIV infection. Their activation results primarily from TLR7-mediated sensing of HIV-infected cells. However, the interactions between HIV-infected T cells and pDCs that modulate this sensing process remain poorly understood. BST2/Tetherin is a restriction factor that inhibits HIV release by cross-linking virions onto infected cell surface. BST2 was also shown to engage the ILT7 pDC-specific inhibitory receptor and repress TLR7/9-mediated IFN-I production by activated pDCs. Here, we show that Vpu, the HIV-1 antagonist of BST2, suppresses TLR7-mediated IFN-I production by pDC through a mechanism that relies on the interaction of BST2 on HIV-producing cells with ILT7. Even though Vpu downregulates surface BST2 as a mean to counteract the restriction on HIV-1 release, we also find that the viral protein re-locates remaining BST2 molecules outside viral assembly sites where they are free to bind and activate ILT7 upon cell-to-cell contact. This study shows that through a targeted regulation of surface BST2, Vpu promotes HIV-1 release and limits pDC antiviral responses upon sensing of infected cells. This mechanism of innate immune evasion is likely to be important for an efficient early viral dissemination during acute infection.
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada.
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Bego
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada.
authors.forename: Édouard
authors.initials: É
authors.lastname: Côté
authors.affiliation: Université Grenoble Alpes, Unit of Virus Host Cell Interactions (UVHCI), CNRS, UVHCI, Grenoble, France.
authors.forename: Nick
authors.initials: N
authors.lastname: Aschman
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada.
authors.forename: Johanne
authors.initials: J
authors.lastname: Mercier
authors.affiliation: Université Grenoble Alpes, Unit of Virus Host Cell Interactions (UVHCI), CNRS, UVHCI, Grenoble, France.
authors.forename: Winfried
authors.initials: W
authors.lastname: Weissenhorn
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada; Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Éric A
authors.initials: ÉA
authors.lastname: Cohen
mesh_terms: D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion / Q000276:immunology; D018613:Microscopy, Confocal; D020239:Receptor Cross-Talk / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D020349:Surface Plasmon Resonance; D054334:Viral Regulatory and Accessory Proteins / Q000276:immunology* / Q000378:metabolism; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D011971:Receptors, Immunologic; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C488262:LILRA4 protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins