HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes. - Institut Pasteur Access content directly
Journal Articles Journal of Virology Year : 2010

HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes.

Milena Hasan
Nathalie Aulner
Françoise Porrot
Christophe Machu
  • Function : Author
Olivier Renaud
Claire Hivroz
Olivier Schwartz
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Nathalie Sol-Foulon
  • Function : Correspondent author
  • PersonId : 867378

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Abstract

The HIV-1 Nef protein is a pathogenic factor modulating the behavior of infected cells. Nef induces actin cytoskeleton changes and impairs cell migration toward chemokines. We further characterized the morphology, cytoskeleton dynamics, and motility of HIV-1-infected lymphocytes. By using scanning electron microscopy, confocal immunofluorescence microscopy, and ImageStream technology, which combines flow cytometry and automated imaging, we report that HIV-1 induces a characteristic remodeling of the actin cytoskeleton. In infected lymphocytes, ruffle formation is inhibited, whereas long, thin filopodium-like protrusions are induced. Cells infected with HIV with nef deleted display a normal phenotype, and Nef expression alone, in the absence of other viral proteins, induces morphological changes. We also used an innovative imaging system to immobilize and visualize living individual cells in suspension. When combined with confocal "axial tomography," this technique greatly enhances three-dimensional optical resolution. With this technique, we confirmed the induction of long filopodium-like structures in unfixed Nef-expressing lymphocytes. The cytoskeleton reorganization induced by Nef is associated with an important impairment of cell movements. The adhesion and spreading of infected cells to fibronectin, their spontaneous motility, and their migration toward chemokines (CXCL12, CCL3, and CCL19) were all significantly decreased. Therefore, Nef induces complex effects on the lymphocyte actin cytoskeleton and cellular morphology, which likely impacts the capacity of infected cells to circulate and to encounter and communicate with bystander cells.

Domains

Parasitology

Dates and versions

pasteur-00458091 , version 1 (19-02-2010)

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Cite

Cinzia Nobile, Dominika Rudnicka, Milena Hasan, Nathalie Aulner, Françoise Porrot, et al.. HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes.. Journal of Virology, 2010, 84 (5), pp.2282-93. ⟨10.1128/JVI.02230-09⟩. ⟨pasteur-00458091⟩
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