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

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

Fecha de publicación online: 25/04/2012 Fecha de publicación en papel: 23 Junio 2012 Revista: Molecular Biology of the Cell

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.

Autores: Gordón-Alonso M, Rocha-Perugini V, Álvarez S, Moreno-Gonzalo O, Ursa A, López-Martín S, Izquierdo-Useros N, Martínez-Picado J, Muñoz-Fernández MÁ, Yáñez-Mó M, Sánchez-Madrid F.

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