Endosome-to-cytosol transport of viral nucleocapsids

Article Article scientifique Article Endosome-to-cytosol transport of viral nucleocapsids eng 2005 author Le Blanc Isabelle 532769 author Luyet Pierre-Philippe 504603 author Pons Véronique 584408 author Ferguson Charles author Emans Neil author Petiot Anne 525183 author Mayran Nathalie 507602 author Demaurex Nicolas 0000-0002-9933-6772 24642 author Faure Julien 514837 author Sadoul Rémy author Parton Robert G author Gruenberg Jean 29661 653-664 10.1038/ncb1269 15951806 1465-7392 During viral infection, fusion of the viral envelope with endosomal membranes and nucleocapsid release were thought to be concomitant events. We show here that for the vesicular stomatitis virus they occur sequentially, at two successive steps of the endocytic pathway. Fusion already occurs in transport intermediates between early and late endosomes, presumably releasing the nucleocapsid within the lumen of intra-endosomal vesicles, where it remains hidden. Transport to late endosomes is then required for the nucleocapsid to be delivered to the cytoplasm. This last step, which initiates infection, depends on the late endosomal lipid lysobisphosphatidic acid (LBPA) and its putative effector Alix/AIP1, and is regulated by phosphatidylinositol-3-phosphate (PtdIns3P) signalling via the PtdIns3P-binding protein Snx16. We conclude that the nucleocapsid is exported into the cytoplasm after the back-fusion of internal vesicles with the limiting membrane of late endosomes, and that this process is controlled by the phospholipids LBPA and PtdIns3P and their effectors. Animals Biological Transport/physiology Cattle Cell Line Cricetinae Cytosol/metabolism/ultrastructure Endosomal Sorting Complexes Required for Transport Endosomes/metabolism/ultrastructure Epithelial Cells/virology Fibroblasts/virology HeLa Cells Humans Lysophospholipids/physiology Membrane Fusion/drug effects/physiology Microscopy, Electron Microscopy, Fluorescence Monoglycerides Nucleocapsid/metabolism Phosphatidylinositol Phosphates/physiology Phosphoproteins/genetics/physiology RNA, Viral/biosynthesis/metabolism Signal Transduction/physiology Sorting Nexins Time Factors Transport Vesicles/metabolism/ultrastructure Vesicular Transport Proteins/genetics/physiology Vesicular stomatitis Indiana virus/physiology Virus Replication/genetics Dewey 540 Dewey 612 39 Département de biochimie 144 134 Département de physiologie cellulaire et métabolisme 21C false 168 Signaux intracellulaires 210 Nature cell biology 7 7 150c5570-19dd-456d-8a0c-60eae57e9b3f Article (Published version) Restricted Endosome-to-cytosol transport of viral nucleocapsids.pdf 2227272 application/pdf restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

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Endosome-to-cytosol transport of viral nucleocapsids	Nature cell biology	2005	704	0

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