Next Article in Journal
Antiseptic Effect of Ps-K18: Mechanism of Its Antibacterial and Anti-Inflammatory Activities
Previous Article in Journal
Myosin Cross-Bridge Behaviour in Contracting Muscle—The T1 Curve of Huxley and Simmons (1971) Revisited
Previous Article in Special Issue
Comparative Genomics, Infectivity and Cytopathogenicity of American Isolates of Zika Virus that Developed Persistent Infections in Human Embryonic Kidney (HEK293) Cells
Open AccessArticle

TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy

Institute of Biophotonics, National Yang-Ming University, Taipei 11221, Taiwan
Brain Research Center, National Yang-Ming University, Taipei 11221, Taiwan
Faculty of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City 22060, Taiwan
Department and Institute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(19), 4893;
Received: 28 August 2019 / Revised: 29 September 2019 / Accepted: 29 September 2019 / Published: 2 October 2019
(This article belongs to the Special Issue Molecular Research on Emerging Mosquito-Transmitted RNA Viruses)
Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin domain 1 (TIM-1) receptor is a putative DENV receptor and promotes apoptotic body clearance by autophagy induction, it raises the possibility that TIM-1 may participate in the activation of DENV-induced autophagy. In this study, confocal images first revealed the co-localization of TIM-1 with autophagosomes in DENV-induced autophagy rather than rapamycin-induced autophagy, suggesting the co-transportation of TIM-1 with DENV during infection. The treatment of siRNA to knockdown TIM-1 expression in DENV-infected GFP-microtubule-associated protein light chain 3 (LC3)-Huh7.5 cells revealed that TIM-1 is required not only for DENV cellular internalization but also for autophagy activation. Furthermore, knockdown p85, a subunit of phosphoinositide 3-kinases (PI3Ks), which is co-localized with TIM-1 at rab5-positive endosomes caused the reduction of autophagy, indicating that TIM-1-mediated DENV-induced autophagy requires p85. Taken together, the current study uncovered TIM-1 as a novel factor for triggering autophagy in DENV infection through TIM-1-p85 axis, in addition to serving as a DENV receptor. View Full-Text
Keywords: dengue virus; autophagy; TIM-1; p85; rab5; early endosome dengue virus; autophagy; TIM-1; p85; rab5; early endosome
Show Figures

Figure 1

MDPI and ACS Style

Chu, L.-W.; Yang, C.-J.; Peng, K.-J.; Chen, P.-L.; Wang, S.-J.; Ping, Y.-H. TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy. Int. J. Mol. Sci. 2019, 20, 4893.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop