title: The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry.
abstract: Syntenin-1 is a cytosolic adaptor protein involved in several cellular processes requiring polarization. Human immunodeficiency virus type 1 (HIV-1) attachment to target CD4(+) T-cells induces polarization of the viral receptor and coreceptor, CD4/CXCR4, and cellular structures toward the virus contact area, and triggers local actin polymerization and phosphatidylinositol 4,5-bisphosphate (PIP(2)) production, which are needed for successful HIV infection. We show that syntenin-1 is recruited to the plasma membrane during HIV-1 attachment and associates with CD4, the main HIV-1 receptor. Syntenin-1 overexpression inhibits HIV-1 production and HIV-mediated cell fusion, while syntenin depletion specifically increases HIV-1 entry. Down-regulation of syntenin-1 expression reduces F-actin polymerization in response to HIV-1. Moreover, HIV-induced PIP(2) accumulation is increased in syntenin-1-depleted cells. Once the virus has entered the target cell, syntenin-1 polarization toward the viral nucleocapsid is lost, suggesting a spatiotemporal regulatory role of syntenin-1 in actin remodeling, PIP(2) production, and the dynamics of HIV-1 entry.
authors.affiliation: Servicio de Inmunología, Instituto de Investigación Sanitaria de la Princesa, Hospital Universitario de la Princesa, 28006 Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Gordón-Alonso
authors.forename: Vera
authors.initials: V
authors.lastname: Rocha-Perugini
authors.forename: Susana
authors.initials: S
authors.lastname: Álvarez
authors.forename: Olga
authors.initials: O
authors.lastname: Moreno-Gonzalo
authors.forename: Angeles
authors.initials: A
authors.lastname: Ursa
authors.forename: Soraya
authors.initials: S
authors.lastname: López-Martín
authors.forename: Nuria
authors.initials: N
authors.lastname: Izquierdo-Useros
authors.forename: Javier
authors.initials: J
authors.lastname: Martínez-Picado
authors.forename: Maria Ángeles
authors.initials: MÁ
authors.lastname: Muñoz-Fernández
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D000199:Actins / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D015726:Giant Cells; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D019169:Jurkat Cells; D018613:Microscopy, Confocal; D009154:Mutation; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D053676:Syntenins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D053586:Virus Internalization
chemical_list: D000199:Actins; D015704:CD4 Antigens; D019269:Phosphatidylinositol 4,5-Diphosphate; D053676:Syntenins; D049452:Green Fluorescent Proteins