title: Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection.
abstract: Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.
authors.affiliation: National Yang-Ming University, Institute of Biophotonics, Taipei, TaiwancNational Yang-Ming University, Biophotonics and Molecular Imaging Research Center, Taipei, Taiwan.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Chu
authors.forename: Yi-Lung
authors.initials: YL
authors.lastname: Huang
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Lee
authors.forename: Long-Ying
authors.initials: LY
authors.lastname: Huang
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Chen
authors.forename: Ya-Hsuan
authors.initials: YH
authors.lastname: Lin
authors.forename: Jyun-Yu
authors.initials: JY
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Xiang
authors.forename: Chau-Hwang
authors.initials: CH
authors.lastname: Lee
authors.forename: Yueh-Hsin
authors.initials: YH
authors.lastname: Ping
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D003715:Dengue / Q000821:virology*; D003716:Dengue Virus / Q000737:chemistry / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D057054:Molecular Imaging / Q000379:methods*; D010588:Phagosomes; D020123:Sirolimus / Q000494:pharmacology; D014771:Virion / Q000737:chemistry / Q000472:pathogenicity / Q000502:physiology
chemical_list: C025946:3-methyladenine; D000225:Adenine; D020123:Sirolimus