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

PLoS Pathogens

Chen Chen¹  Xiaowei Zhuang¹  Heidi van der Ende-Metselaar²  Jan Wilschut²  Hilde M. van der Schaar²  Michael J. Rust³  Jolanda M. Smit⁴ 

[1] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, United States of America;Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;Department of Molecular and Cell Biology, Harvard University, Cambridge, Massachusetts, United States of America;Department of Physics, Harvard University, Cambridge, Massachusetts, United States of America

关键词: Endosomes;    Dengue virus;    Membrane fusion;    Viral entry;    Endocytosis;    Fluorescence imaging;    Chlorpromazine;    Yellow fluorescent protein;   

DOI  :  10.1371/journal.ppat.1000244

学科分类：生物科学（综合）

来源: Public Library of Science

【 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.

【 授权许可】

CC BY