Abstract
Results Here, we examined the migration ability of HIV-1infected primary human macrophages. We show that HIV-1 infection modifies dramatically the migration of macrophages in 3-dimentionnal (3D) environments. While the amoeboid migration mode is inhibited upon infection, another migration mode specifically used by macrophages in dense 3D environments, the mesenchymal migration mode, is greatly enhanced. HIV-1 negative factor (Nef) is responsible for both effects on macrophage migration modes. Consistently with an increase in mesenchymal migration capacities, Nef accumulates around F-actin structures necessary for proteolysis of the extracellular matrix, e.g. podosomes, and alters their structure, function and dynamics. Mechanistically, HIV-1-induced podosome modifications and mesenchymal macrophage migration depend on Nef’s ability to activate the macrophage-specific Src tyrosine kinase, Hck.
Highlights
Macrophages are a cell target of Human Immunodeficiency Virus-1 (HIV-1)
We show that HIV-1 infection modifies dramatically the migration of macrophages in 3-dimentionnal (3D) environments
While the amoeboid migration mode is inhibited upon infection, another migration mode used by macrophages in dense 3D environments, the mesenchymal migration mode, is greatly enhanced
Summary
HIV-1 Nef alters podosomes and promotes the mesenchymal migration in human macrophages. Christel Vérollet1,2*, Emilie Bonnaud, Cassandre Kinnaer, Renaud Poincloux, Annabelle Corjeon, Isabelle Maridonneau-Parini. From Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts Cambridge, UK. From Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts Cambridge, UK. 16-18 September 2013
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