The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry

• Published in: Molecular biology of the cell Vol. 23; no. 12; pp. 2253 - 2263
• Main Authors: Gordón-Alonso, Mónica, Rocha-Perugini, Vera, Álvarez, Susana, Moreno-Gonzalo, Olga, Ursa, Angeles, López-Martín, Soraya, Izquierdo-Useros, Nuria, Martínez-Picado, Javier, Muñoz-Fernández, Maria Ángeles, Yáñez-Mó, María, Sánchez-Madrid, Francisco
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 15.06.2012
• Series: A Highlights from
• Subjects: Actins - metabolism; CD4 Antigens - metabolism; Cell Fusion; Cell Line; Cell Line, Tumor; Cell Membrane - metabolism; Giant Cells; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; HIV-1 - metabolism; HIV-1 - physiology; Host-Pathogen Interactions; Humans; Immunoblotting; Immunoprecipitation; Jurkat Cells; Microscopy, Confocal; Mutation; Phosphatidylinositol 4,5-Diphosphate - metabolism; Protein Binding; RNA Interference; Syntenins - genetics; Syntenins - metabolism; T-Lymphocytes - metabolism; T-Lymphocytes - virology; Virus Internalization
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.e11-12-1003

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.