Inhibition of phagocytosis in HIV-1-infected macrophages relies on Nef-dependent alteration of focal delivery of recycling compartments

Julie Mazzolini, Floriane Herit, Jerome Bouchet, Alexandre Benmerah, Serge Benichou, Florence Niedergang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Phagocytosis in macrophages is receptor mediated and relies on actin polymerization coordinated with 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 endo-some recruitment was inhibited in HIV-1-infected cells. Expression of negative factor (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 vesicle-associated membrane protein (VAMP3)- and tumor necrosis factor-alpha (TNF alpha)-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 function down-regulation in infected cells. (Blood. 2010; 115(21): 4226-4236)

Original languageEnglish
Pages (from-to)4226-4236
Number of pages11
JournalBlood
Volume115
Issue number21
DOIs
Publication statusPublished - 27 May 2010

Keywords / Materials (for Non-textual outputs)

  • VIRUS TYPE-1 NEF
  • MONOCYTE-DERIVED MACROPHAGES
  • HIV-1 NEF
  • MEDIATED PHAGOCYTOSIS
  • ENDOPLASMIC-RETICULUM
  • MEMBRANE DYNAMICS
  • CELL BIOLOGY
  • INFECTION
  • AP-1
  • MECHANISM

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