TIM-1 Ubiquitination Mediates Dengue Virus Entry
Summary: Dengue virus (DENV) is a major human pathogen causing millions of infections yearly. Despite intensive investigations, a DENV receptor that directly participates in virus internalization has not yet been characterized. Here, we report that the phosphatidylserine receptor TIM-1 is an authent...
Main Authors: | , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2018-05-01
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Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718305424 |
id |
doaj-e9342707f6bf4b168845c0906c68bef1 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ophélie Dejarnac Mohamed Lamine Hafirassou Maxime Chazal Margaux Versapuech Julien Gaillard Manuel Perera-Lecoin Claudia Umana-Diaz Lucie Bonnet-Madin Xavier Carnec Jean-Yves Tinevez Constance Delaugerre Olivier Schwartz Philippe Roingeard Nolwenn Jouvenet Clarisse Berlioz-Torrent Laurent Meertens Ali Amara |
spellingShingle |
Ophélie Dejarnac Mohamed Lamine Hafirassou Maxime Chazal Margaux Versapuech Julien Gaillard Manuel Perera-Lecoin Claudia Umana-Diaz Lucie Bonnet-Madin Xavier Carnec Jean-Yves Tinevez Constance Delaugerre Olivier Schwartz Philippe Roingeard Nolwenn Jouvenet Clarisse Berlioz-Torrent Laurent Meertens Ali Amara TIM-1 Ubiquitination Mediates Dengue Virus Entry Cell Reports |
author_facet |
Ophélie Dejarnac Mohamed Lamine Hafirassou Maxime Chazal Margaux Versapuech Julien Gaillard Manuel Perera-Lecoin Claudia Umana-Diaz Lucie Bonnet-Madin Xavier Carnec Jean-Yves Tinevez Constance Delaugerre Olivier Schwartz Philippe Roingeard Nolwenn Jouvenet Clarisse Berlioz-Torrent Laurent Meertens Ali Amara |
author_sort |
Ophélie Dejarnac |
title |
TIM-1 Ubiquitination Mediates Dengue Virus Entry |
title_short |
TIM-1 Ubiquitination Mediates Dengue Virus Entry |
title_full |
TIM-1 Ubiquitination Mediates Dengue Virus Entry |
title_fullStr |
TIM-1 Ubiquitination Mediates Dengue Virus Entry |
title_full_unstemmed |
TIM-1 Ubiquitination Mediates Dengue Virus Entry |
title_sort |
tim-1 ubiquitination mediates dengue virus entry |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-05-01 |
description |
Summary: Dengue virus (DENV) is a major human pathogen causing millions of infections yearly. Despite intensive investigations, a DENV receptor that directly participates in virus internalization has not yet been characterized. Here, we report that the phosphatidylserine receptor TIM-1 is an authentic DENV entry receptor that plays an active role in virus endocytosis. Genetic ablation of TIM-1 strongly impaired DENV infection. Total internal reflection fluorescence microscopy analyses of live infected cells show that TIM-1 is mostly confined in clathrin-coated pits and is co-internalized with DENV during viral entry. TIM-1 is ubiquitinated at two lysine residues of its cytoplasmic domain, and this modification is required for DENV endocytosis. Furthermore, STAM-1, a component of the ESCRT-0 complex involved in intracellular trafficking of ubiquitinated cargos, interacts with TIM-1 and is required for DENV infection. Overall, our results show that TIM-1 is the first bona fide receptor identified for DENV. : Dejarnac et al. find that the phosphatidylserine receptor TIM-1 is a bona fide DENV receptor that mediates virus uptake through the clathrin-mediated pathway. TIM-1 is ubiquitinated at two lysines in its cytoplasmic tail and interacts with STAM-1 for efficient DENV infection. |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718305424 |
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spelling |
doaj-e9342707f6bf4b168845c0906c68bef12020-11-24T21:55:00ZengElsevierCell Reports2211-12472018-05-0123617791793TIM-1 Ubiquitination Mediates Dengue Virus EntryOphélie Dejarnac0Mohamed Lamine Hafirassou1Maxime Chazal2Margaux Versapuech3Julien Gaillard4Manuel Perera-Lecoin5Claudia Umana-Diaz6Lucie Bonnet-Madin7Xavier Carnec8Jean-Yves Tinevez9Constance Delaugerre10Olivier Schwartz11Philippe Roingeard12Nolwenn Jouvenet13Clarisse Berlioz-Torrent14Laurent Meertens15Ali Amara16INSERM U944-CNRS 7212, Laboratoire de Pathologie et Virologie Moléculaire, Institut Universitaire d’Hématologie, Université Paris Diderot Sorbonne Paris Cité, Hôpital St. Louis, 75475 Paris Cedex 10, FranceINSERM U944-CNRS 7212, Laboratoire de Pathologie et Virologie Moléculaire, Institut Universitaire d’Hématologie, Université Paris Diderot Sorbonne Paris Cité, Hôpital St. Louis, 75475 Paris Cedex 10, FranceViral Genomics and Vaccination Unit, UMR-3569 CNRS, Pasteur Institute, 75724 Paris, FranceLaboratoire Interaction Hôte-Virus, Institut Cochin, INSERM U1016-CNRS UMR8104-Université Paris Descartes, 75014 Paris, FranceINSERM U966 MAVIVH, Faculté de Médecine, Université de Tours, Tours, FranceINSERM U944-CNRS 7212, Laboratoire de Pathologie et Virologie Moléculaire, Institut Universitaire d’Hématologie, Université Paris Diderot Sorbonne Paris Cité, Hôpital St. Louis, 75475 Paris Cedex 10, FranceINSERM U944-CNRS 7212, Laboratoire de Pathologie et Virologie Moléculaire, Institut Universitaire d’Hématologie, Université Paris Diderot Sorbonne Paris Cité, Hôpital St. Louis, 75475 Paris Cedex 10, FranceINSERM U944-CNRS 7212, Laboratoire de Pathologie et Virologie Moléculaire, Institut Universitaire d’Hématologie, Université Paris Diderot Sorbonne Paris Cité, Hôpital St. Louis, 75475 Paris Cedex 10, FranceINSERM U944-CNRS 7212, Laboratoire de Pathologie et Virologie Moléculaire, Institut Universitaire d’Hématologie, Université Paris Diderot Sorbonne Paris Cité, Hôpital St. Louis, 75475 Paris Cedex 10, FranceInstitut Pasteur, Citech, UTechS PBI, 75724 Paris Cedex 15, FranceDepartement des Maladies Infectieuses, Hôpital Saint Louis, 75010 Paris, FranceUnité Virus et Immunité, Institut Pasteur, 75724 Paris, FranceINSERM U966 MAVIVH, Faculté de Médecine, Université de Tours, Tours, FranceViral Genomics and Vaccination Unit, UMR-3569 CNRS, Pasteur Institute, 75724 Paris, FranceLaboratoire Interaction Hôte-Virus, Institut Cochin, INSERM U1016-CNRS UMR8104-Université Paris Descartes, 75014 Paris, FranceINSERM U944-CNRS 7212, Laboratoire de Pathologie et Virologie Moléculaire, Institut Universitaire d’Hématologie, Université Paris Diderot Sorbonne Paris Cité, Hôpital St. Louis, 75475 Paris Cedex 10, France; Corresponding authorINSERM U944-CNRS 7212, Laboratoire de Pathologie et Virologie Moléculaire, Institut Universitaire d’Hématologie, Université Paris Diderot Sorbonne Paris Cité, Hôpital St. Louis, 75475 Paris Cedex 10, France; Corresponding authorSummary: Dengue virus (DENV) is a major human pathogen causing millions of infections yearly. Despite intensive investigations, a DENV receptor that directly participates in virus internalization has not yet been characterized. Here, we report that the phosphatidylserine receptor TIM-1 is an authentic DENV entry receptor that plays an active role in virus endocytosis. Genetic ablation of TIM-1 strongly impaired DENV infection. Total internal reflection fluorescence microscopy analyses of live infected cells show that TIM-1 is mostly confined in clathrin-coated pits and is co-internalized with DENV during viral entry. TIM-1 is ubiquitinated at two lysine residues of its cytoplasmic domain, and this modification is required for DENV endocytosis. Furthermore, STAM-1, a component of the ESCRT-0 complex involved in intracellular trafficking of ubiquitinated cargos, interacts with TIM-1 and is required for DENV infection. Overall, our results show that TIM-1 is the first bona fide receptor identified for DENV. : Dejarnac et al. find that the phosphatidylserine receptor TIM-1 is a bona fide DENV receptor that mediates virus uptake through the clathrin-mediated pathway. TIM-1 is ubiquitinated at two lysines in its cytoplasmic tail and interacts with STAM-1 for efficient DENV infection.http://www.sciencedirect.com/science/article/pii/S2211124718305424 |