TIM-1 Ubiquitination Mediates Dengue Virus Entry

被引：83

作者：

Dejarnac, Ophelie ^{[1
,3
]}

Hafirassou, Mohamed Lamine ^{[1
,3
]}

Chazal, Maxime ^{[2
]}

Versapuech, Margaux ^{[3
]}

Gaillard, Julien ^{[4
]}

Perera-Lecoin, Manuel ^{[1
]}

Umana-Diaz, Claudia ^{[1
]}

Bonnet-Madin, Lucie ^{[1
]}

Carnec, Xavier ^{[1
]}

Tinevez, Jean-Yves ^{[5
]}

Delaugerre, Constance ^{[6
]}

Schwartz, Olivier ^{[7
]}

Roingeard, Philippe ^{[4
]}

Jouvenet, Nolwenn ^{[2
]}

Berlioz-Torrent, Clarisse ^{[3
]}

Meertens, Laurent ^{[1
]}

Amara, Ali ^{[1
]}

机构：

[1] Univ Paris Diderot, Sorbonne Paris Cite, Hop St Louis, Inst Univ Hematol,INSERM U944,CNRS 7212,Lab Patho, F-75475 Paris 10, France

[2] Pasteur Inst, UMR 3569, Viral Genom & Vaccinat Unit, CNRS, F-75724 Paris, France

[3] Univ Paris 05, INSERM U1016, CNRS UMR8104, Lab Interact Hote Virus,Inst Cochin, F-75014 Paris, France

[4] Univ Tours, Fac Med, INSERM MAVIVH U966, Tours, France

[5] UTechS PBI, Citech, Inst Pasteur, F-75724 Paris 15, France

[6] Hop St Louis, Dept Malad Infect, F-75010 Paris, France

[7] Inst Pasteur, Unite Virus & Immunite, F-75724 Paris, France

来源：

CELL REPORTS | 2018年 / 23卷 / 06期

关键词：

T-CELL IMMUNOGLOBULIN; PHOSPHATIDYLSERINE RECEPTORS; APOPTOTIC MIMICRY; IMMUNE-RESPONSES; DENDRITIC CELLS; CD300A BINDS; INFECTION; INNATE; PHOSPHATIDYLETHANOLAMINE; NONINTEGRIN;

D O I：

10.1016/j.celrep.2018.04.013

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1779 / 1793

页数：15

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