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TIM-1 Ubiquitination Mediates Dengue Virus Entry

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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https://hal.archives-ouvertes.fr/hal-02327431
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Ophélie Dejarnac, Mohamed Lamine Hafirassou, Maxime Chazal, Margaux Versapuech, Julien Gaillard, et al.. TIM-1 Ubiquitination Mediates Dengue Virus Entry. Cell Reports , Elsevier Inc, 2018, 23 (6), pp.1779-1793. ⟨10.1016/j.celrep.2018.04.013⟩. ⟨hal-02327431⟩

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