2. Academic Validation
  3. TIM-1 Ubiquitination Mediates Dengue Virus Entry

TIM-1 Ubiquitination Mediates Dengue Virus Entry

  • Cell Rep. 2018 May 8;23(6):1779-1793. doi: 10.1016/j.celrep.2018.04.013.
Ophélie Dejarnac 1,  Mohamed Lamine Hafirassou 1,  Maxime Chazal 2,  Margaux Versapuech 3,  Julien Gaillard 4,  Manuel Perera-Lecoin 1,  Claudia Umana-Diaz 1,  Lucie Bonnet-Madin 1,  Xavier Carnec 1,  Jean-Yves Tinevez 5,  Constance Delaugerre 6,  Olivier Schwartz 7,  Philippe Roingeard 4,  Nolwenn Jouvenet 2,  Clarisse Berlioz-Torrent 3,  Laurent Meertens 8,  Ali Amara 9
Affiliations

Affiliations

  • 1 INSERM 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.
  • 2 Viral Genomics and Vaccination Unit, UMR-3569 CNRS, Pasteur Institute, 75724 Paris, France.
  • 3 Laboratoire Interaction Hôte-Virus, Institut Cochin, INSERM U1016-CNRS UMR8104-Université Paris Descartes, 75014 Paris, France.
  • 4 INSERM U966 MAVIVH, Faculté de Médecine, Université de Tours, Tours, France.
  • 5 Institut Pasteur, Citech, UTechS PBI, 75724 Paris Cedex 15, France.
  • 6 Departement des Maladies Infectieuses, Hôpital Saint Louis, 75010 Paris, France.
  • 7 Unité Virus et Immunité, Institut Pasteur, 75724 Paris, France.
  • 8 INSERM 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. Electronic address: [email protected].
  • 9 INSERM 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. Electronic address: [email protected].
PMID: 29742433 DOI: 10.1016/j.celrep.2018.04.013
Abstract

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.

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