Inhibition of phagocytosis in HIV-1 infected macrophages relies on Nef-dependent alteration of focal delivery of recycling compartments
- Julie Mazzolini1,
- Floriane Herit2,
- Jérôme Bouchet1,
- Alexandre Benmerah1,
- Serge Benichou1, and
- Florence Niedergang1,*
- 1 Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris, France;
- 2 Inserm, U1016, Paris, France
- * Corresponding author; email: florence.niedergang{at}inserm.fr
Abstract
Phagocytosis in macrophages is receptor-mediated and relies on actin polymerization coordinated a the focal delivery of intracellular membranes that is necessary for optimal phagocytosis of large particles. Here we show that phagocytosis by various receptors was inhibited in primary human macrophages infected with wild type HIV-1 but not with a nef-deleted virus. We observed no major perturbation of F-actin accumulation but adaptor protein 1 (AP1)-positive endosome recruitment was inhibited in HIV-1-infected cells. Expression of Nef was sufficient to inhibit phagocytosis, and myristoylation, as well as the LL and DD motifs involved in association of Nef with AP complexes were important for this inhibition. We observed that Nef interferes with AP1 in association with membranes and/or with a cleaved regulatory form of AP1. Finally, an alteration of the recruitment of VAMP3- and TNFα-positive recycling endosomes regulated by AP1, but not of VAMP7-positive late endosomes, was observed in phagocytic cups of HIV-1-infected macrophages. We conclude that HIV-1 impairs optimal phagosome formation through Nef-dependent perturbation of the endosomal remodeling relying on AP1. We therefore identified a mechanism of macrophage functions downregulation in infected cells.
- Submitted December 15, 2009.
- Accepted March 1, 2010.
- Copyright © 2005 American Society of Hematology
