期刊
CELL REPORTS
卷 23, 期 6, 页码 1779-1793出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.04.013
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类别
资金
- French government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases' [ANR-10-LABX-62-IBEID]
- CHIKV-Viro-Immuno project [ANR-14-CE14-0015-01]
- TIMTAMDEN project [ANR-14-CE14-0029]
- Fondation pour la Recherche Medicale
- ANR
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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