Article abstract
Nature Cell Biology 7, 653 - 664 (2005)
Published online: 12 June 2005 | doi:10.1038/ncb1269
Endosome-to-cytosol transport of viral nucleocapsids
Isabelle Le Blanc1,2,9, Pierre-Philippe Luyet1,9, Véronique Pons1, Charles Ferguson3, Neil Emans4, Anne Petiot1,5, Nathalie Mayran1,6, Nicolas Demaurex7, Julien Fauré8, Rémy Sadoul8, Robert G. Parton3 & J. Gruenberg1
Abstract
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 (PtdIns(3)P) signalling via the PtdIns(3)P-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 PtdIns(3)P and their effectors.
- Biochemistry Department, University of Geneva, 30 quai E. Ansermet, 1211 Geneva 4, Switzerland.
- Department of Molecular and Cell Biology, 16 Barker Hall, University of California, Berkeley, CA 94720-3202, USA.
- Institute for Molecular Bioscience, Center for Microscopy and Microanalysis, and School of Biomedical Sciences, University of Queensland, Queensland 4072, Australia.
- Pasteur Institute, 39-1, Howolgok-Dong, Seongbuk-gu, Seoul 136-791, Korea.
- Unité INSERM 504, 16 Ave P.V. Couturier, 94807 Villejuif cedex, France.
- Institute of Experimental Pathology, 25 Rue du Bugnon, 1011 Lausanne, Switzerland.
- Department of Physiology, Centre Médical Universitaire, rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
- Neurodégénérescence et Plasticité, Inserm-Université Joseph Fourier, Hôpital A. Michallon, 38043 Grenoble Cedex 9, France.
- These authors contributed equally to this work.
Correspondence to: J. Gruenberg1 e-mail: jean.gruenberg@biochem.unige.ch
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Viral entry: a detour through multivesicular bodiesNature Cell Biology News and Views (01 Jul 2005)
GGAing ubiquitin to the endosomeNature Cell Biology News and Views (01 Mar 2004)
See all 4 matches for News And ViewsRESEARCH
Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cellsThe EMBO Journal Article (01 Sep 2000)
See all 28 matches for Research
