Journal
SCIENCE ADVANCES
Volume 5, Issue 10, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aax0821
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Funding
- Cell and Tissue Imaging Facility (PICT-IBiSA), Institut Curie [ANR10-INBS-04]
- CNRS
- INSERM
- Universite Paris Descartes
- Agence Nationale de la Recherche [2011 BSV3 025 02]
- Agence Nationale de Recherches sur le Sida et les Hepatites (ANRS) [AO2012-2]
- Fondation pour la Recherche Medicale [FRM DEQ20130326518]
- Investissements d'Avenir program [ANR-10-LABX-62-IBEID, ANR-10-IDEX-0001-02 PSL]
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Using a cell-based assay monitoring differential protein transport in the secretory pathway coupled to high-content screening, we have identified three molecules that specifically reduce the delivery of the major co-receptor for HIV-1, CCR5, to the plasma membrane. They have no effect on the closely related receptors CCR1 and CXCR4. These molecules are also potent in primary macrophages as they markedly decrease HIV entry. At the molecular level, two of these molecules inhibit the critical palmitoylation of CCR5 and thereby block CCR5 in the early secretory pathway. Our results open a clear therapeutics avenue based on trafficking control and demonstrate that preventing HIV infection can be performed at the level of its receptor delivery.
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