Dissecting the Cell Entry Pathway of Dengue Virus by Single-Particle Tracking in Living Cells

被引:378
作者
van der Schaar, Hilde M. [1 ]
Rust, Michael J. [2 ]
Chen, Chen [3 ]
van der Ende-Metselaar, Heidi [1 ]
Wilschut, Jan [1 ]
Zhuang, Xiaowei [3 ,4 ,5 ]
Smit, Jolanda M. [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Mol Virol Sect, Dept Med Microbiol, Groningen, Netherlands
[2] Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA
[3] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA
[4] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA
[5] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1371/journal.ppat.1000244
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Dengue virus (DENV) is an enveloped RNA virus that causes the most common arthropod-borne infection worldwide. The mechanism by which DENV infects the host cell remains unclear. In this work, we used live-cell imaging and single-virus tracking to investigate the cell entry, endocytic trafficking, and fusion behavior of DENV. Simultaneous tracking of DENV particles and various endocytic markers revealed that DENV enters cells exclusively via clathrin-mediated endocytosis. The virus particles move along the cell surface in a diffusive manner before being captured by a pre-existing clathrin-coated pit. Upon clathrin-mediated entry, DENV particles are transported to Rab5-positive endosomes, which subsequently mature into late endosomes through acquisition of Rab7 and loss of Rab5. Fusion of the viral membrane with the endosomal membrane was primarily detected in late endosomal compartments.
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页数:9
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