Source:http://linkedlifedata.com/resource/pubmed/id/20299515
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
21
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pubmed:dateCreated |
2010-5-28
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pubmed:abstractText |
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 endosome 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 (TNFalpha)-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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Protein Complex 1,
http://linkedlifedata.com/resource/pubmed/chemical/R-SNARE Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/VAMP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/VAMP7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicle-Associated Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/nef Gene Products, Human...,
http://linkedlifedata.com/resource/pubmed/chemical/nef protein, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1528-0020
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
27
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pubmed:volume |
115
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4226-36
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pubmed:meshHeading |
pubmed-meshheading:20299515-Actins,
pubmed-meshheading:20299515-Adaptor Protein Complex 1,
pubmed-meshheading:20299515-Animals,
pubmed-meshheading:20299515-Cell Compartmentation,
pubmed-meshheading:20299515-Cell Line,
pubmed-meshheading:20299515-Endosomes,
pubmed-meshheading:20299515-Gene Deletion,
pubmed-meshheading:20299515-Genes, nef,
pubmed-meshheading:20299515-HIV-1,
pubmed-meshheading:20299515-Humans,
pubmed-meshheading:20299515-Macrophages,
pubmed-meshheading:20299515-Mice,
pubmed-meshheading:20299515-Models, Biological,
pubmed-meshheading:20299515-Phagocytosis,
pubmed-meshheading:20299515-R-SNARE Proteins,
pubmed-meshheading:20299515-Vesicle-Associated Membrane Protein 3,
pubmed-meshheading:20299515-nef Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2010
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pubmed:articleTitle |
Inhibition of phagocytosis in HIV-1-infected macrophages relies on Nef-dependent alteration of focal delivery of recycling compartments.
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pubmed:affiliation |
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (Unite Mixte de Recherche 8104), Paris, France.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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