title: The ESCRT-I subunit TSG101 controls endosome-to-cytosol release of viral RNA.
abstract: Like other enveloped viruses, vesicular stomatitis virus infects cells through endosomes. There, the viral envelope undergoes fusion with endosomal membranes, thereby releasing the nucleocapsid into the cytoplasm and allowing infection to proceed. Previously, we reported that the viral envelope fuses preferentially with the membrane of vesicles present within multivesicular endosomes. Then, these intra-endosomal vesicles (containing nucleocapsids) are transported to late endosomes, where back-fusion with the endosome limiting membrane delivers the nucleocapsid into the cytoplasm. In this study, we show that the tumor susceptibility gene 101 (Tsg101) subunit of the endosomal sorting complexes required for transport (ESCRT)-I complex, which mediates receptor sorting into multivesicular endosomes, is dispensable for viral envelope fusion with endosomal membranes and viral RNA transport to late endosomes but is necessary for infection. Our data indicate that Tsg101, in contrast to the ESCRT-0 component Hrs, plays a direct role in nucleocapsid release from within multivesicular endosomes to the cytoplasm, presumably by controlling the back-fusion process. We conclude that Tsg101, through selective interactions with its partners including Hrs and Alix, may link receptor sorting and lysosome targeting to the back-fusion process involved in viral capsid release.
authors.affiliation: Department of Biochemistry, University of Geneva, 30 quai E. Ansermet, 1211 Geneva 4, Switzerland.
authors.forename: Pierre-Philippe
authors.initials: PP
authors.lastname: Luyet
authors.forename: Thomas
authors.initials: T
authors.lastname: Falguières
authors.forename: Véronique
authors.initials: V
authors.lastname: Pons
authors.forename: Asit K
authors.initials: AK
authors.lastname: Pattnaik
authors.forename: Jean
authors.initials: J
authors.lastname: Gruenberg
mesh_terms: D000818:Animals; D001692:Biological Transport; D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D021122:Protein Subunits / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018116:Vesiculovirus / Q000378:metabolism / Q000648:ultrastructure; D053586:Virus Internalization; D000099177:Tsg101 Protein
chemical_list: D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D021122:Protein Subunits; D012367:RNA, Viral; D014157:Transcription Factors; D000099177:Tsg101 Protein